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Sample records for regulator rcac require

  1. Informational requirements for transcriptional regulation.

    PubMed

    O'Neill, Patrick K; Forder, Robert; Erill, Ivan

    2014-05-01

    Transcription factors (TFs) regulate transcription by binding to specific sites in promoter regions. Information theory provides a useful mathematical framework to analyze the binding motifs associated with TFs but imposes several assumptions that limit their applicability to specific regulatory scenarios. Explicit simulations of the co-evolution of TFs and their binding motifs allow the study of the evolution of regulatory networks with a high degree of realism. In this work we analyze the impact of differential regulatory demands on the information content of TF-binding motifs by means of evolutionary simulations. We generalize a predictive index based on information theory, and we validate its applicability to regulatory scenarios in which the TF binds significantly to the genomic background. Our results show a logarithmic dependence of the evolved information content on the occupancy of target sites and indicate that TFs may actively exploit pseudo-sites to modulate their occupancy of target sites. In regulatory networks with differentially regulated targets, we observe that information content in TF-binding motifs is dictated primarily by the fraction of total probability mass that the TF assigns to its target sites, and we provide a predictive index to estimate the amount of information associated with arbitrarily complex regulatory systems. We observe that complex regulatory patterns can exert additional demands on evolved information content, but, given a total occupancy for target sites, we do not find conclusive evidence that this effect is because of the range of required binding affinities. PMID:24689750

  2. Informational Requirements for Transcriptional Regulation

    PubMed Central

    O'Neill, Patrick K.; Forder, Robert

    2014-01-01

    Abstract Transcription factors (TFs) regulate transcription by binding to specific sites in promoter regions. Information theory provides a useful mathematical framework to analyze the binding motifs associated with TFs but imposes several assumptions that limit their applicability to specific regulatory scenarios. Explicit simulations of the co-evolution of TFs and their binding motifs allow the study of the evolution of regulatory networks with a high degree of realism. In this work we analyze the impact of differential regulatory demands on the information content of TF-binding motifs by means of evolutionary simulations. We generalize a predictive index based on information theory, and we validate its applicability to regulatory scenarios in which the TF binds significantly to the genomic background. Our results show a logarithmic dependence of the evolved information content on the occupancy of target sites and indicate that TFs may actively exploit pseudo-sites to modulate their occupancy of target sites. In regulatory networks with differentially regulated targets, we observe that information content in TF-binding motifs is dictated primarily by the fraction of total probability mass that the TF assigns to its target sites, and we provide a predictive index to estimate the amount of information associated with arbitrarily complex regulatory systems. We observe that complex regulatory patterns can exert additional demands on evolved information content, but, given a total occupancy for target sites, we do not find conclusive evidence that this effect is because of the range of required binding affinities. PMID:24689750

  3. EPA regulations require close study

    SciTech Connect

    Wilkins, J.D.

    1981-08-03

    The time to review environmental legislation and to pinpoint unreasonable or unnecessary sections is when the proposed regulation is published in the Federal Register before it becomes law. Four oil and gas industry organizations can help track and evaluate environmental regulations: the A.G.A.'s Environmental Coordination Group, the Interstate Natural Gas Association of America (INGAA) Environmental Subcommittee, the Gulf Coast Environmental Affairs Group, and the Houston Environmental Roundtable. Besides acting as a watchdog, the industry must perform independent studies to provide valid data for writing the regulations. Once the laws are passed, the industry has no choice but to comply; a plea of ignorance will not change the situation.

  4. Regulations which require employee training: An overview

    SciTech Connect

    Gilfus, L.J.

    1995-11-01

    In order to identify the Occupational Safety and Health Administration (OSHA) regulations which apply to a certain plant or facility, one needs to find the reference materials that are needed and that can be trusted. An overview is presented of the following: Title 29 -- Labor, OSHA Training Requirements; Title 40, Environmental Protection Agency Training Requirements; and Title 49, Department of Transportation Training Regulations.

  5. MAPPING GASOLINE REQUIREMENTS, APPLICABLE REGULATIONS AND BANS

    EPA Science Inventory

    Federal and State regulations play an important role in understanding gasoline composition around the United States. Multiple sources of information on these programs were used to develop reliable, up-to-date maps showing gasoline requirements imposed by various regulations. Th...

  6. 77 FR 51784 - Federal Acquisition Regulation; Information Collection; Qualification Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-27

    ... minutes per submission assuming an offeror's use of electronic information tracking and retrieval... Regulation; Information Collection; Qualification Requirements AGENCY: Department of Defense (DOD), General... reinstatement request for an information collection requirement regarding an existing OMB clearance....

  7. 77 FR 12754 - Contractor Legal Management Requirements; Acquisition Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-02

    ... Energy Acquisition Regulation (DEAR) (76 FR 81408). The comment period is reopened until March 16, 2012... published a NOPR in the Federal Register (76 FR 81408) to revise existing regulations covering contractor... Part 719 48 Parts 931, 952 and 970 RIN 1990-AA37 Contractor Legal Management Requirements;...

  8. General requirements for RCRA regulated hazardous waste tanks

    SciTech Connect

    1995-11-01

    The Resource Conservation and Recovery Act (RCRA), as amended, requires that tanks used for the storage or treatment of hazardous waste (HazW) be permitted, and comply with the requirements contained within the Code of Federal Regulations (CFR) TItle 40 in Subpart J of Part 264/265, unless those tanks have been exempted. Subpart J specifies requirements for the design, construction, installation, operation, inspection, maintenance, repair, release, response, and closure of HazW tanks. Also, the regulations make a distinction between new and existing tanks. Effective December 6, 1995, standards for controlling volatile organic air emissions will apply to non-exempt HazW tanks. HazW tanks will have to be equipped with a cover or floating roof, or be designed to operate as a closed system, to be in compliance with the air emission control requirements. This information brief describes those tanks that are subject to the Subpart J requirements, and will also discuss secondary containment, inspection, restrictions on waste storage, release response, and closure requirements associated with regulated HazW tanks.

  9. 40 CFR 63.312 - Existing regulations and requirements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... National Emission Standards for Coke Oven Batteries § 63.312 Existing regulations and requirements. (a) The..., topside port lids, coke oven doors, and charging operations in effect on September 15, 1992, or which have... method of monitoring in effect on September 15, 1992, and that ensures coke oven emission...

  10. 40 CFR 63.312 - Existing regulations and requirements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... National Emission Standards for Coke Oven Batteries § 63.312 Existing regulations and requirements. (a) The..., topside port lids, coke oven doors, and charging operations in effect on September 15, 1992, or which have... method of monitoring in effect on September 15, 1992, and that ensures coke oven emission...

  11. 40 CFR 63.312 - Existing regulations and requirements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... National Emission Standards for Coke Oven Batteries § 63.312 Existing regulations and requirements. (a) The..., topside port lids, coke oven doors, and charging operations in effect on September 15, 1992, or which have... method of monitoring in effect on September 15, 1992, and that ensures coke oven emission...

  12. 40 CFR 63.312 - Existing regulations and requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... National Emission Standards for Coke Oven Batteries § 63.312 Existing regulations and requirements. (a) The..., topside port lids, coke oven doors, and charging operations in effect on September 15, 1992, or which have... method of monitoring in effect on September 15, 1992, and that ensures coke oven emission...

  13. 40 CFR 63.312 - Existing regulations and requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... National Emission Standards for Coke Oven Batteries § 63.312 Existing regulations and requirements. (a) The..., topside port lids, coke oven doors, and charging operations in effect on September 15, 1992, or which have... method of monitoring in effect on September 15, 1992, and that ensures coke oven emission...

  14. 76 FR 22070 - Federal Acquisition Regulation; Service Contracts Reporting Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-20

    ...DoD, GSA, and NASA are proposing to amend the Federal Acquisition Regulation (FAR) to implement section 743 of Division C of the Consolidated Appropriations Act, 2010. This proposed rule amends the FAR to require service contractors for executive agencies, except the Department of Defense (DoD), covered by the Federal Activities Inventory Reform (FAIR) Act of 1998, to submit information......

  15. 78 FR 80369 - Federal Acquisition Regulation; Service Contracts Reporting Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-31

    ...DoD, GSA, and NASA are issuing a final rule amending the Federal Acquisition Regulation (FAR) to implement a section of the Consolidated Appropriations Act, 2010. This final rule amends the FAR to require service contractors for executive agencies, except where DoD has fully funded the contract or order, to submit information annually in support of agency-level inventories for service......

  16. Review of orders and regulations requiring environmental protection

    SciTech Connect

    Kelly, E.; Cunningham, R.; Michael, D.

    1996-09-01

    With the increased awareness of and interest in potential ecological risks associated with past, current, and future Department of Energy (DOE) activities, DOE`s Defense Programs (DP) Office of Technical and Environmental Support sponsored a study to (1) evaluate the effectiveness of the current compliance-driven environmental protection and assessment efforts relative to ecological concerns; (2) explore the need for a more focused, integrated approach to address ecological impacts; and (3) identify the requirements for an integrated approach. The study explored four questions. (a) Which federal regulations and DOE orders either explicitly require ecological assessments or implicitly require them through environmental protection language? (b) What currently is being done at selected DOE facilities to implement these regulations and orders? (c) What are private sector industries doing in terms of ecological risk assessments and how do industry approaches and issues compare with those of DOE? (d) What, if anything, in addition to current efforts is needed to ensure the protection of ecological resources associated with DOE facilities, to support defensible decision making, and to improve efficiency? The results of this study are presented in a report titled {open_quotes}Integrated, Comprehensive Ecological Impact Assessments In Support of Department of Energy Decision Making{close_quotes}. This report is a companion document to that report. This report provides a more detailed discussion of the document reviews of the relevant environmental protection regulations and current and pending DOE orders. The main goal of the document reviews was to understand existing requirements for ecological data collection and impact assessments.

  17. Actin is required for IFT regulation in Chlamydomonas reinhardtii

    PubMed Central

    Avasthi, Prachee; Onishi, Masayuki; Karpiak, Joel; Yamamoto, Ryosuke; Mackinder, Luke; Jonikas, Martin C.; Sale, Winfield S.; Shoichet, Brian; Pringle, John R.; Marshall, Wallace F.

    2014-01-01

    Summary Assembly of cilia and flagella requires intraflagellar transport (IFT), a highly regulated kinesin-based transport system that moves cargo from the basal body to the tip of flagella [1]. The recruitment of IFT components to basal bodies is a function of flagellar length, with increased recruitment in rapidly growing short flagella [2]. The molecular pathways regulating IFT are largely a mystery. Since actin network disruption leads to changes in ciliary length and number, actin has been proposed to have a role in ciliary assembly. However, the mechanisms involved are unknown. In Chlamydomonas reinhardtii, conventional actin is found in both the cell body and the inner dynein arm complexes within flagella [3, 4]. Previous work showed that treating Chlamydomonas cells with the actin-depolymerizing compound cytochalasin D resulted in reversible flagellar shortening [5], but how actin is related to flagellar length or assembly remains unknown. Here, we utilize small-molecule inhibitors and genetic mutants to analyze the role of actin dynamics in flagellar assembly in Chlamydomonas reinhardtii. We demonstrate that actin plays a role in IFT recruitment to basal bodies during flagellar elongation, and that when actin is perturbed, the normal dependence of IFT recruitment on flagellar length is lost. We also find that actin is required for sufficient entry of IFT material into flagella during assembly. These same effects are recapitulated with a myosin inhibitor suggesting actin may act via myosin in a pathway by which flagellar assembly is regulated by flagellar length. PMID:25155506

  18. Actin is required for IFT regulation in Chlamydomonas reinhardtii.

    PubMed

    Avasthi, Prachee; Onishi, Masayuki; Karpiak, Joel; Yamamoto, Ryosuke; Mackinder, Luke; Jonikas, Martin C; Sale, Winfield S; Shoichet, Brian; Pringle, John R; Marshall, Wallace F

    2014-09-01

    Assembly of cilia and flagella requires intraflagellar transport (IFT), a highly regulated kinesin-based transport system that moves cargo from the basal body to the tip of flagella [1]. The recruitment of IFT components to basal bodies is a function of flagellar length, with increased recruitment in rapidly growing short flagella [2]. The molecular pathways regulating IFT are largely a mystery. Because actin network disruption leads to changes in ciliary length and number, actin has been proposed to have a role in ciliary assembly. However, the mechanisms involved are unknown. In Chlamydomonas reinhardtii, conventional actin is found in both the cell body and the inner dynein arm complexes within flagella [3, 4]. Previous work showed that treating Chlamydomonas cells with the actin-depolymerizing compound cytochalasin D resulted in reversible flagellar shortening [5], but how actin is related to flagellar length or assembly remains unknown. Here we utilize small-molecule inhibitors and genetic mutants to analyze the role of actin dynamics in flagellar assembly in Chlamydomonas reinhardtii. We demonstrate that actin plays a role in IFT recruitment to basal bodies during flagellar elongation and that when actin is perturbed, the normal dependence of IFT recruitment on flagellar length is lost. We also find that actin is required for sufficient entry of IFT material into flagella during assembly. These same effects are recapitulated with a myosin inhibitor, suggesting that actin may act via myosin in a pathway by which flagellar assembly is regulated by flagellar length. PMID:25155506

  19. 75 FR 6186 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Part 205...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-08

    ... Defense Acquisition Regulations System Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Part 205, Publicizing Contract Actions AGENCY: Defense Acquisition Regulations System... approved information collection requirement. SUMMARY: In compliance with Section 3506(c)(2)(A) of...

  20. 75 FR 12518 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Part 237...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-16

    ... Defense Acquisition Regulations System Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Part 237, Service Contracting AGENCY: Defense Acquisition Regulations System... approved information collection requirement. SUMMARY: In compliance with Section 3506(c)(2)(A) of...

  1. 78 FR 15935 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement (DFARS...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-13

    ... Defense Acquisition Regulations System Information Collection Requirement; Defense Federal Acquisition Regulation Supplement (DFARS); Bonds and Insurance AGENCY: Defense Acquisition Regulations System, Department... approved information collection requirement. SUMMARY: In compliance with Section 3506(c)(2)(A) of...

  2. 76 FR 50461 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Types of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-15

    ... Defense Acquisition Regulations System Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Types of Contracts AGENCY: Defense Acquisition Regulations System, Department of... information collection requirement. SUMMARY: In compliance with Section 3506(c)(2)(A) of the...

  3. 75 FR 20825 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; DoD Pilot...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-21

    ... Defense Acquisition Regulations System Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; DoD Pilot Mentor-Protege Program AGENCY: Defense Acquisition Regulations System... approved information collection requirement. ] SUMMARY: In compliance with section 3506(c)(2)(A) of...

  4. 75 FR 20825 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Part 211...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-21

    ... Defense Acquisition Regulations System Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Part 211, Describing Agency Needs AGENCY: Defense Acquisition Regulations System... approved information collection requirement. SUMMARY: In compliance with Section 3506(c)(2)(A) of...

  5. 78 FR 70025 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-22

    ... Defense Acquisition Regulations System Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Subcontracting Policies and Procedures AGENCY: Defense Acquisition Regulations System... approved information collection requirement. SUMMARY: In compliance with section 3506(c)(2)(A) of...

  6. 77 FR 30998 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Government...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-24

    ... Defense Acquisition Regulations System Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Government Property AGENCY: Defense Acquisition Regulations System, Department of... and Technical Information System,'' and is used when directed by the plant clearance officer. e....

  7. 77 FR 43076 - Federal Acquisition Regulation; Information Collection; Value Engineering Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-23

    ... Regulation; Information Collection; Value Engineering Requirements AGENCIES: Department of Defense (DOD... approved information collection requirement concerning Value Engineering Requirements. Public comments are...: Submit comments identified by Information Collection 9000- 0027, Value Engineering Requirements, by...

  8. 75 FR 45104 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Contract...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-02

    ... Defense Acquisition Regulations System Information Collection Requirement; Defense Federal Acquisition... Regulations System, Department of Defense (DoD). ACTION: Notice and request for comments. SUMMARY: In... announces the proposed extension of a public information collection requirement and seeks public comment...

  9. 75 FR 68331 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; DFARS Part...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-05

    ... Defense Acquisition Regulations System Information Collection Requirement; Defense Federal Acquisition... Acquisition Regulations System, Department of Defense (DoD). ACTION: Notice and request for comments regarding a proposed extension of an approved information collection requirement. SUMMARY: In compliance...

  10. 75 FR 26739 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Part 244...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-12

    ... Defense Acquisition Regulations System Information Collection Requirement; Defense Federal Acquisition...: Defense Acquisition Regulations System, Department of Defense. ACTION: Notice and request for comments regarding a proposed extension of an approved information collection requirement. SUMMARY: In...

  11. 78 FR 17186 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement (DFARS...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-20

    ... Defense Acquisition Regulations System Information Collection Requirement; Defense Federal Acquisition... Acquisition Regulations System, Department of Defense (DoD). ACTION: Notice and request for comments regarding a proposed extension of an approved information collection requirement. SUMMARY: In compliance...

  12. 75 FR 10790 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-09

    ... Regulation Supplement; Notification Requirements for Critical Safety Items AGENCY: Defense Acquisition... Supplement (DFARS) Notification Requirements for Critical Safety Items; OMB Control Number 0704-0441....

  13. Thyroid hormone is required for hypothalamic neurons regulating cardiovascular functions

    PubMed Central

    Mittag, Jens; Lyons, David J.; Sällström, Johan; Vujovic, Milica; Dudazy-Gralla, Susi; Warner, Amy; Wallis, Karin; Alkemade, Anneke; Nordström, Kristina; Monyer, Hannah; Broberger, Christian; Arner, Anders; Vennström, Björn

    2012-01-01

    Thyroid hormone is well known for its profound direct effects on cardiovascular function and metabolism. Recent evidence, however, suggests that the hormone also regulates these systems indirectly through the central nervous system. While some of the molecular mechanisms underlying the hormone’s central control of metabolism have been identified, its actions in the central cardiovascular control have remained enigmatic. Here, we describe a previously unknown population of parvalbuminergic neurons in the anterior hypothalamus that requires thyroid hormone receptor signaling for proper development. Specific stereotaxic ablation of these cells in the mouse resulted in hypertension and temperature-dependent tachycardia, indicating a role in the central autonomic control of blood pressure and heart rate. Moreover, the neurons exhibited intrinsic temperature sensitivity in patch-clamping experiments, providing a new connection between cardiovascular function and core temperature. Thus, the data identify what we believe to be a novel hypothalamic cell population potentially important for understanding hypertension and indicate developmental hypothyroidism as an epigenetic risk factor for cardiovascular disorders. Furthermore, the findings may be beneficial for treatment of the recently identified patients that have a mutation in thyroid hormone receptor α1. PMID:23257356

  14. translin Is Required for Metabolic Regulation of Sleep.

    PubMed

    Murakami, Kazuma; Yurgel, Maria E; Stahl, Bethany A; Masek, Pavel; Mehta, Aradhana; Heidker, Rebecca; Bollinger, Wesley; Gingras, Robert M; Kim, Young-Joon; Ja, William W; Suter, Beat; DiAngelo, Justin R; Keene, Alex C

    2016-04-01

    Dysregulation of sleep or feeding has enormous health consequences. In humans, acute sleep loss is associated with increased appetite and insulin insensitivity, while chronically sleep-deprived individuals are more likely to develop obesity, metabolic syndrome, type II diabetes, and cardiovascular disease. Conversely, metabolic state potently modulates sleep and circadian behavior; yet, the molecular basis for sleep-metabolism interactions remains poorly understood. Here, we describe the identification of translin (trsn), a highly conserved RNA/DNA binding protein, as essential for starvation-induced sleep suppression. Strikingly, trsn does not appear to regulate energy stores, free glucose levels, or feeding behavior suggesting the sleep phenotype of trsn mutant flies is not a consequence of general metabolic dysfunction or blunted response to starvation. While broadly expressed in all neurons, trsn is transcriptionally upregulated in the heads of flies in response to starvation. Spatially restricted rescue or targeted knockdown localizes trsn function to neurons that produce the tachykinin family neuropeptide Leucokinin. Manipulation of neural activity in Leucokinin neurons revealed these neurons to be required for starvation-induced sleep suppression. Taken together, these findings establish trsn as an essential integrator of sleep and metabolic state, with implications for understanding the neural mechanism underlying sleep disruption in response to environmental perturbation. PMID:27020744

  15. Discovery of a Splicing Regulator Required for Cell Cycle Progression

    SciTech Connect

    Suvorova, Elena S.; Croken, Matthew; Kratzer, Stella; Ting, Li-Min; Conde de Felipe, Magnolia; Balu, Bharath; Markillie, Lye Meng; Weiss, Louis M.; Kim, Kami; White, Michael W.

    2013-02-01

    In the G1 phase of the cell division cycle, eukaryotic cells prepare many of the resources necessary for a new round of growth including renewal of the transcriptional and protein synthetic capacities and building the machinery for chromosome replication. The function of G1 has an early evolutionary origin and is preserved in single and multicellular organisms, although the regulatory mechanisms conducting G1 specific functions are only understood in a few model eukaryotes. Here we describe a new G1 mutant from an ancient family of apicomplexan protozoans. Toxoplasma gondii temperature-sensitive mutant 12-109C6 conditionally arrests in the G1 phase due to a single point mutation in a novel protein containing a single RNA-recognition-motif (TgRRM1). The resulting tyrosine to asparagine amino acid change in TgRRM1 causes severe temperature instability that generates an effective null phenotype for this protein when the mutant is shifted to the restrictive temperature. Orthologs of TgRRM1 are widely conserved in diverse eukaryote lineages, and the human counterpart (RBM42) can functionally replace the missing Toxoplasma factor. Transcriptome studies demonstrate that gene expression is downregulated in the mutant at the restrictive temperature due to a severe defect in splicing that affects both cell cycle and constitutively expressed mRNAs. The interaction of TgRRM1 with factors of the tri-SNP complex (U4/U6 & U5 snRNPs) indicate this factor may be required to assemble an active spliceosome. Thus, the TgRRM1 family of proteins is an unrecognized and evolutionarily conserved class of splicing regulators. This study demonstrates investigations into diverse unicellular eukaryotes, like the Apicomplexa, have the potential to yield new insights into important mechanisms conserved across modern eukaryotic kingdoms.

  16. 77 FR 67366 - Federal Acquisition Regulation; Information Collection; Quality Assurance Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-09

    ... Regulation; Information Collection; Quality Assurance Requirements AGENCY: Department of Defense (DOD... information collection requirement concerning quality assurance requirements. Public comments are particularly... and methodology; ways to enhance the quality, utility, and clarity of the information to be...

  17. 78 FR 60898 - Regulation on Definition and Requirements for a Nationally Recognized Testing Laboratory...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-02

    ...OSHA requests comments concerning its proposed revision and extension of the information collection requirements specified by its Regulation at 29 CFR 1910.7, ``definition and requirements for a nationally recognized testing laboratory'' (The Regulation). The Regulation specifies procedures that organizations must follow to apply for, and to maintain, OSHA's recognition to test and certify......

  18. 78 FR 19467 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement (DFARS...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-01

    ... Defense Acquisition Regulations System Information Collection Requirement; Defense Federal Acquisition Regulation Supplement (DFARS); DoD Pilot Mentor-Prot g Program AGENCY: Defense Acquisition Regulations System... approved information collection requirement. SUMMARY: In compliance with Section 3506(c)(2)(A) of...

  19. 78 FR 63462 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-24

    ... organizational conflicts of interest arising in a systems engineering and technical assistance contract for an... Defense Acquisition Regulations System Information Collection Requirement; Defense Federal Acquisition...: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION: Notice and request...

  20. 76 FR 72914 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Government...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-28

    ... Defense Acquisition Regulations System Information Collection Requirement; Defense Federal Acquisition... Foreign Disclosure and Technical Information System,'' and is used when directed by the plant clearance... Regulations System, Department of Defense (DoD). ACTION: Notice and request for comments. SUMMARY:...

  1. 75 FR 68333 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; DFARS...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-05

    ... Defense Acquisition Regulations System Information Collection Requirement; Defense Federal Acquisition...-0248) AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION: Notice and request for comments regarding a proposed extension of an approved information collection...

  2. 75 FR 41161 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Part 251...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-15

    ... Defense Acquisition Regulations System Information Collection Requirement; Defense Federal Acquisition... vehicles under the Interagency Fleet Management System (IFMS) and obtain related services. The information... Regulations System, Department of Defense (DoD). ACTION: Notice and request for comments regarding a...

  3. 76 FR 35424 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-17

    ... Regulation Supplement; Acquisition of Information Technology AGENCY: Defense Acquisition Regulations System... technology. The Office of Management and Budget (OMB) has approved this information collection requirement... Supplement (DFARS) Part 239, Acquisition of Information Technology, and the associated clauses at DFARS...

  4. 78 FR 25795 - Contractor Legal Management Requirements; Acquisition Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-03

    ... Federal Register on August 31, 1994 (59 FR 44981). The interim Acquisition Letter was finalized as a Policy Statement on April 3, 1996 (61 FR 14763). This Policy Statement was followed by a formal... Regulations with an effective date of April 23, 2001 (66 FR 4616, 66 FR 19717). After a decade operating...

  5. Cholesterol and regulated exocytosis: a requirement for unitary exocytotic events.

    PubMed

    Rituper, Boštjan; Flašker, Ajda; Guček, Alenka; Chowdhury, Helena H; Zorec, Robert

    2012-01-01

    Since the 1970s, much effort was been expended researching mechanisms of regulated exocytosis. Early work focused mainly on the role of proteins. Most notably the discovery of SNARE proteins in the 1980s and the zippering hypothesis brought us much closer to understanding the complex interactions in membrane fusion between vesicle and plasma membranes, a pivotal component of regulated exocytosis. However, most likely due to the predictions of the Singer-Nicholson fluid mosaic membrane model, the lipid components of the exocytotic machinery remained largely overlooked. Lipids were considered passive constituents of cellular membranes, not contributing much, if anything, to the process of exocytosis and membrane fusion. Since the 1990s, this so-called proteocentric view has been gradually giving way to the new perspective best described with the term proteolipidic. Many lipids were found to be of great importance in the regulation of exocytosis. Here we highlight the role of cholesterol. Furthermore, by using high-resolution cell-attached membrane capacitance measurements, we have monitored unitary exocytotic events in cholesterol-depleted membranes. We show that the frequency of these events is attenuated, providing evidence at the single vesicle level that cholesterol directly influences the merger of the vesicle and the plasma membranes. PMID:22726879

  6. 78 FR 68831 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement (DFARS...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-15

    ... Defense Acquisition Regulations System Information Collection Requirement; Defense Federal Acquisition... System, Department of Defense (DoD). ACTION: Notice and request for comments regarding a proposed extension of an approved information collection requirement. SUMMARY: In compliance with Section...

  7. 78 FR 67133 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-08

    ... holders further disseminate the information to other firms within a geographic area defined in the... Defense Acquisition Regulations System Information Collection Requirement; Defense Federal Acquisition... approved information collection requirement. SUMMARY: In compliance with Section 3506(c)(2)(A) of...

  8. 7 CFR 318.13-3 - General requirements for all regulated articles.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 5 2011-01-01 2011-01-01 false General requirements for all regulated articles. 318.13-3 Section 318.13-3 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE STATE OF HAWAII AND TERRITORIES QUARANTINE NOTICES Regulated Articles From Hawaii and...

  9. 49 CFR 195.11 - What is a regulated rural gathering line and what requirements apply?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false What is a regulated rural gathering line and what...) PIPELINE SAFETY TRANSPORTATION OF HAZARDOUS LIQUIDS BY PIPELINE General § 195.11 What is a regulated rural gathering line and what requirements apply? Each operator of a regulated rural gathering line, as defined...

  10. 49 CFR 390.11 - Motor carrier to require observance of driver regulations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 5 2010-10-01 2010-10-01 false Motor carrier to require observance of driver regulations. 390.11 Section 390.11 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL MOTOR CARRIER SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION FEDERAL MOTOR CARRIER SAFETY REGULATIONS FEDERAL MOTOR CARRIER...

  11. 49 CFR 379.11 - Waiver of requirements of the regulations in this part.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 5 2010-10-01 2010-10-01 false Waiver of requirements of the regulations in this part. 379.11 Section 379.11 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL MOTOR CARRIER SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION FEDERAL MOTOR CARRIER SAFETY REGULATIONS PRESERVATION OF RECORDS §...

  12. 77 FR 24611 - Removal of Regulations Requiring 3% Withholding by Government Entities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-25

    ... 9524, 76 FR 26583, 2011-23 IRB 843) (the May 2011 final regulations). Those regulations were issued to... in the Federal Register on May 9, 2011 (REG-151687-10, 76 FR 26678, 2011-23 IRB 867). A related... Internal Revenue Service 26 CFR Part 31 RIN 1545-BK83 Removal of Regulations Requiring 3% Withholding...

  13. 77 FR 29983 - Federal Acquisition Regulation; Information Collection; Novation/Change of Name Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-21

    ... Regulation; Information Collection; Novation/ Change of Name Requirements AGENCY: Department of Defense (DOD... collection requirement concerning Novation/Change of Name Requirements. Public comments are particularly... comments identified by Information Collection 9000- 0076, Novation/Change of Name Requirements, by any...

  14. 76 FR 35218 - Federal Acquisition Regulation; Information Collection; Cost or Pricing Data Requirements and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-16

    ... Regulation; Information Collection; Cost or Pricing Data Requirements and Information Other Than Cost or... requirement concerning cost or pricing data requirements and information other than cost or pricing data... Information Collection 9000- 0013, Cost or Pricing Data Requirements and Information Other Than Cost...

  15. 76 FR 71558 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Requests...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-18

    ... Defense Acquisition Regulations System Information Collection Requirement; Defense Federal Acquisition... Acquisition Regulations System, Department of Defense (DoD). ACTION: Notice and request for comments. SUMMARY...), DoD announces the proposed extension of a public information collection requirement and seeks...

  16. 49 CFR 1220.5 - Waiver of requirements of these regulations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 9 2010-10-01 2010-10-01 false Waiver of requirements of these regulations. 1220.5 Section 1220.5 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION BOARD, DEPARTMENT OF TRANSPORTATION (CONTINUED) ACCOUNTS, RECORDS AND REPORTS PRESERVATION OF RECORDS § 1220.5 Waiver of requirements...

  17. 76 FR 71707 - Revising Underground Storage Tank Regulations-Revisions to Existing Requirements and New...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-18

    ...EPA is proposing to make certain revisions to the 1988 underground storage tank (UST) technical, financial responsibility, and state program approval regulations. These changes establish federal requirements that are similar to key portions of the Energy Policy Act of 2005; they also update certain 1988 UST regulations. Proposed changes include: Adding secondary containment requirements for......

  18. 77 FR 62495 - Federal Acquisition Regulation; Submission for OMB Review; Novation/Change of Name Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-15

    ... approved information collection requirement concerning Novation/Change of Name Requirements. A notice was published in the Federal Register at 77 FR 29983, on May 21, 2012. One respondent submitted comments. Public... Regulation; Submission for OMB Review; Novation/Change of Name Requirements AGENCY: Department of...

  19. 75 FR 60263 - Federal Acquisition Regulation; Offering a Construction Requirement-8(a) Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-29

    ... Federal Acquisition Regulation; Offering a Construction Requirement--8(a) Program AGENCIES: Department of... submitting offering letters to SBA for a construction requirement for which a specific offeror is nominated... offerings for construction ] requirements be submitted to the SBA District Office for the geographical...

  20. 78 FR 25445 - Federal Acquisition Regulation; Submission for OMB Review; Quality Assurance Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-01

    ... information collection requirement concerning quality assurance requirements. A notice was published in the Federal Register at 77 FR 67366, on November 11, 2012. No comments were received. DATES: Submit comments... Regulation; Submission for OMB Review; Quality Assurance Requirements AGENCY: Department of Defense...

  1. 12 CFR 749.5 - Format for records required by other NCUA regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Format for records required by other NCUA regulations. 749.5 Section 749.5 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS RECORDS PRESERVATION PROGRAM AND APPENDICES-RECORD RETENTION GUIDELINES; CATASTROPHIC...

  2. 78 FR 72620 - Federal Acquisition Regulation; Higher-Level Contract Quality Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-03

    ... comment in the Federal Register at 78 FR 28780 on May 16, 2013. 2. FAR Case 2013-002, entitled ``Expanded... RIN 9000-AM65 Federal Acquisition Regulation; Higher-Level Contract Quality Requirements AGENCY... Acquisition Regulation (FAR) to clarify when to use higher-level quality standards in solicitations...

  3. 27 CFR 70.411 - Imposition of taxes, qualification requirements, and regulations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... operation of distilled spirits plants. Part 19 of title 27 CFR contains the regulations relating to the...) Miscellaneous liquor transactions. Part 29 of 27 CFR contains miscellaneous regulations relative to the... requirements therefor. (3) (4) Gauging of distilled spirits. Part 30 of title 27 CFR contains the...

  4. 27 CFR 70.411 - Imposition of taxes, qualification requirements, and regulations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... operation of distilled spirits plants. Part 19 of title 27 CFR contains the regulations relating to the...) Miscellaneous liquor transactions. Part 29 of 27 CFR contains miscellaneous regulations relative to the... requirements therefor. (3) (4) Gauging of distilled spirits. Part 30 of title 27 CFR contains the...

  5. 27 CFR 70.411 - Imposition of taxes, qualification requirements, and regulations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... operation of distilled spirits plants. Part 19 of title 27 CFR contains the regulations relating to the...) Miscellaneous liquor transactions. Part 29 of 27 CFR contains miscellaneous regulations relative to the... requirements therefor. (3) (4) Gauging of distilled spirits. Part 30 of title 27 CFR contains the...

  6. 27 CFR 70.411 - Imposition of taxes, qualification requirements, and regulations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... operation of distilled spirits plants. Part 19 of title 27 CFR contains the regulations relating to the...) Miscellaneous liquor transactions. Part 29 of 27 CFR contains miscellaneous regulations relative to the... requirements therefor. (3) (4) Gauging of distilled spirits. Part 30 of title 27 CFR contains the...

  7. 49 CFR 390.11 - Motor carrier to require observance of driver regulations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 5 2011-10-01 2011-10-01 false Motor carrier to require observance of driver... Motor carrier to require observance of driver regulations. Whenever in part 325 of subchapter A or in this subchapter a duty is prescribed for a driver or a prohibition is imposed upon the driver, it...

  8. 49 CFR 390.11 - Motor carrier to require observance of driver regulations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 5 2012-10-01 2012-10-01 false Motor carrier to require observance of driver... Motor carrier to require observance of driver regulations. Whenever in part 325 of subchapter A or in this subchapter a duty is prescribed for a driver or a prohibition is imposed upon the driver, it...

  9. 49 CFR 390.11 - Motor carrier to require observance of driver regulations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 5 2013-10-01 2013-10-01 false Motor carrier to require observance of driver... Motor carrier to require observance of driver regulations. Whenever in part 325 of subchapter A or in this subchapter a duty is prescribed for a driver or a prohibition is imposed upon the driver, it...

  10. 49 CFR 390.11 - Motor carrier to require observance of driver regulations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 5 2014-10-01 2014-10-01 false Motor carrier to require observance of driver... Motor carrier to require observance of driver regulations. Whenever in part 325 of subchapter A or in this subchapter a duty is prescribed for a driver or a prohibition is imposed upon the driver, it...

  11. 12 CFR 350.12 - Disclosure required by applicable banking or securities law or regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 4 2011-01-01 2011-01-01 false Disclosure required by applicable banking or securities law or regulations. 350.12 Section 350.12 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION... STATE NONMEMBER BANKS § 350.12 Disclosure required by applicable banking or securities law...

  12. 76 FR 72915 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; DoD...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-28

    ... Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; DoD Acquisition Process (Various Miscellaneous Requirements) (OMB Control Number 0704-0187) AGENCY: Department of Defense (DoD... Paperwork Reduction Act of 1995 (44 U.S.C. chapter 35), DoD announces the proposed extension of a...

  13. 12 CFR 350.12 - Disclosure required by applicable banking or securities law or regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Disclosure required by applicable banking or securities law or regulations. 350.12 Section 350.12 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION... STATE NONMEMBER BANKS § 350.12 Disclosure required by applicable banking or securities law...

  14. 75 FR 14448 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-25

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Clinical Trial Requirements... announcing a public workshop entitled ``FDA Clinical Trial Requirements, Regulations, Compliance, and Good... representatives. The program will focus on the relationships among the FDA and clinical trial staff,...

  15. 77 FR 59139 - Prompt Corrective Action, Requirements for Insurance, and Promulgation of NCUA Rules and Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-26

    ... amended by IRPS 03-2, and two NCUA regulations that apply asset thresholds to grant relief from risk-based...'' credit union for determining whether risk-based net worth requirements apply, and 12 CFR 741.3(b)(5)(i... interest rate risk rule requirements. \\1\\ IRPS 03-2, 68 FR 31949 (May 29, 2003). B. Why is the...

  16. 78 FR 4725 - Escrow Requirements Under the Truth in Lending Act (Regulation Z)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-22

    ...The Bureau of Consumer Financial Protection (Bureau) is publishing a final rule that amends Regulation Z (Truth in Lending) to implement certain amendments to the Truth in Lending Act made by the Dodd-Frank Wall Street Reform and Consumer Protection Act (Dodd-Frank Act). Regulation Z currently requires creditors to establish escrow accounts for higher-priced mortgage loans secured by a first......

  17. Pre-LTP requires extracellular signal-regulated kinase in the ACC.

    PubMed

    Yamanaka, Manabu; Tian, Zhen; Darvish-Ghane, Soroush; Zhuo, Min

    2016-02-01

    The extracellular signal-regulated kinase is an important protein kinase for cortical plasticity. Long-term potentiation in the anterior cingulate cortex is believed to play important roles in chronic pain, fear, and anxiety. Previous studies of extracellular signal-regulated kinase are mainly focused on postsynaptic form of long-term potentiation (post-long-term potentiation). Little is known about the relationship between extracellular signal-regulated kinase and presynaptic long-term potentiation (pre-long-term potentiation) in cortical synapses. In this study, we examined whether pre-long-term potentiation in the anterior cingulate cortex requires the activation of presynaptic extracellular signal-regulated kinase. We found that p42/p44 mitogen-activated protein kinase inhibitors, PD98059 and U0126, suppressed the induction of pre-long-term potentiation. By contrast, these inhibitors did not affect the maintenance of pre-long-term potentiation. Using pharmacological inhibitors, we found that pre-long-term potentiation recorded for 1 h did not require transcriptional or translational processes. Our results strongly indicate that the activation of presynaptic extracellular signal-regulated kinase is required for the induction of pre-long-term potentiation, and this involvement may explain the contribution of extracellular signal-regulated kinase to mood disorders. PMID:27178245

  18. Pre-LTP requires extracellular signal-regulated kinase in the ACC

    PubMed Central

    Yamanaka, Manabu; Tian, Zhen; Darvish-Ghane, Soroush

    2016-01-01

    The extracellular signal-regulated kinase is an important protein kinase for cortical plasticity. Long-term potentiation in the anterior cingulate cortex is believed to play important roles in chronic pain, fear, and anxiety. Previous studies of extracellular signal-regulated kinase are mainly focused on postsynaptic form of long-term potentiation (post-long-term potentiation). Little is known about the relationship between extracellular signal-regulated kinase and presynaptic long-term potentiation (pre-long-term potentiation) in cortical synapses. In this study, we examined whether pre-long-term potentiation in the anterior cingulate cortex requires the activation of presynaptic extracellular signal-regulated kinase. We found that p42/p44 mitogen-activated protein kinase inhibitors, PD98059 and U0126, suppressed the induction of pre-long-term potentiation. By contrast, these inhibitors did not affect the maintenance of pre-long-term potentiation. Using pharmacological inhibitors, we found that pre-long-term potentiation recorded for 1 h did not require transcriptional or translational processes. Our results strongly indicate that the activation of presynaptic extracellular signal-regulated kinase is required for the induction of pre-long-term potentiation, and this involvement may explain the contribution of extracellular signal-regulated kinase to mood disorders. PMID:27178245

  19. 26 CFR 56.6001-1 - Notice or regulations requiring records, statements, and special returns.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 17 2011-04-01 2011-04-01 false Notice or regulations requiring records, statements, and special returns. 56.6001-1 Section 56.6001-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES (CONTINUED) PUBLIC CHARITY EXCISE...

  20. 26 CFR 56.6001-1 - Notice or regulations requiring records, statements, and special returns.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 17 2010-04-01 2010-04-01 false Notice or regulations requiring records, statements, and special returns. 56.6001-1 Section 56.6001-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES (CONTINUED) PUBLIC CHARITY EXCISE...

  1. 13 CFR 120.1511 - Certification and other reporting and notification requirements for Other Regulated SBLCs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Certification and other reporting and notification requirements for Other Regulated SBLCs. 120.1511 Section 120.1511 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Risk-Based Lender Oversight Enforcement Actions §...

  2. 50 CFR 14.254 - What are the requirements contained in these regulations?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 1 2010-10-01 2010-10-01 false What are the requirements contained in these regulations? 14.254 Section 14.254 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR TAKING, POSSESSION, TRANSPORTATION, SALE, PURCHASE, BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND...

  3. 9 CFR 201.4 - Bylaws, rules and regulations, and requirements of exchanges, associations, or other...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Bylaws, rules and regulations, and requirements of exchanges, associations, or other organizations; applicability, establishment. 201.4 Section 201.4 Animals and Animal Products GRAIN INSPECTION, PACKERS AND STOCKYARDS ADMINISTRATION (PACKERS...

  4. 78 FR 11279 - Loan Originator Compensation Requirements Under the Truth in Lending Act (Regulation Z)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-15

    ...The Bureau of Consumer Financial Protection (Bureau) is amending Regulation Z to implement amendments to the Truth in Lending Act (TILA) made by the Dodd-Frank Wall Street Reform and Consumer Protection Act (Dodd-Frank Act). The final rule implements requirements and restrictions imposed by the Dodd-Frank Act concerning loan originator compensation; qualifications of, and registration or......

  5. 78 FR 4788 - Regulated Navigation Area; Reporting Requirements for Barges Loaded With Certain Dangerous...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-23

    ...The Commander, Ninth Coast Guard District is staying (suspending) reporting requirements under the Regulated Navigation Area (RNA) established for barges loaded with certain dangerous cargoes (CDC barges) in the inland rivers of the Ninth Coast Guard District. This stay (suspension) extension is necessary because the Coast Guard continues to analyze future reporting needs and evaluate possible......

  6. 78 FR 61183 - Regulated Navigation Area; Reporting Requirements for Barges Loaded With Certain Dangerous...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-03

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA11 Regulated Navigation Area; Reporting Requirements for Barges Loaded With Certain Dangerous Cargoes, Inland Rivers, Ninth Coast Guard District; Stay (Suspension) AGENCY: Coast Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Commander, Ninth Coast...

  7. 76 FR 1360 - Regulated Navigation Area; Reporting Requirements for Barges Loaded With Certain Dangerous...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-10

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA11 Regulated Navigation Area; Reporting Requirements for Barges Loaded With Certain Dangerous Cargoes, Inland Rivers, Eighth Coast Guard District; Stay (Suspension) AGENCY: Coast Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Commander, Eighth...

  8. 21 CFR 16.24 - Regulatory hearing required by the act or a regulation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Regulatory hearing required by the act or a regulation. 16.24 Section 16.24 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL REGULATORY HEARING BEFORE THE FOOD AND DRUG ADMINISTRATION Initiation of Proceedings §...

  9. 2 CFR 25.200 - Requirements for program announcements, regulations, and application instructions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 2 Grants and Agreements 1 2012-01-01 2012-01-01 false Requirements for program announcements, regulations, and application instructions. 25.200 Section 25.200 Grants and Agreements Office of Management and Budget Guidance for Grants and Agreements OFFICE OF MANAGEMENT AND BUDGET GOVERNMENTWIDE GUIDANCE FOR GRANTS AND AGREEMENTS...

  10. 78 FR 73104 - Federal Travel Regulation (FTR); Agency Requirements for Payment of Expenses Connected With the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-05

    ... Heroes Act,'' dated September 12, 2011, and published in the Federal Register (76 FR 57621), delegates to...] RIN 3090-AJ37 Federal Travel Regulation (FTR); Agency Requirements for Payment of Expenses Connected.... General Services Administration (GSA). ACTION: Final rule. ] SUMMARY: GSA is amending the Federal...

  11. 50 CFR 25.23 - What are the general regulations and information collection requirements?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 8 2011-10-01 2011-10-01 false What are the general regulations and information collection requirements? 25.23 Section 25.23 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) THE NATIONAL WILDLIFE REFUGE SYSTEM ADMINISTRATIVE PROVISIONS Administrative Provisions §...

  12. 50 CFR 25.23 - What are the general regulations and information collection requirements?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false What are the general regulations and information collection requirements? 25.23 Section 25.23 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) THE NATIONAL WILDLIFE REFUGE SYSTEM ADMINISTRATIVE PROVISIONS Administrative Provisions §...

  13. 75 FR 29456 - Acquisition Regulation: Subchapter E-General Contracting Requirements, Subchapter F-Special...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-26

    ...The Department of Energy (DOE) is amending the Department of Energy Acquisition Regulation (DEAR) Subchapters E--General Contracting Requirements, F--Special Categories of Contracting, and G--Contract Management to make changes to conform to the FAR, remove out-of-date coverage, and to update references. Today's rule does not alter substantive rights or obligations under current...

  14. 75 FR 964 - Acquisition Regulation: Subchapter E-General Contracting Requirements, Subchapter F-Special...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-07

    ...The Department of Energy (DOE) is proposing to amend the Department of Energy Acquisition Regulation (DEAR) Subchapters E-- General Contracting Requirements, F--Special Categories of Contracting, and G--Contract Management to make changes to conform to the FAR, remove out-of-date coverage, and to update references. DOE will separately propose rules for changes to parts 927 and 945,......

  15. 2 CFR 25.200 - Requirements for program announcements, regulations, and application instructions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 2 Grants and Agreements 1 2014-01-01 2014-01-01 false Requirements for program announcements, regulations, and application instructions. 25.200 Section 25.200 Grants and Agreements Office of Management and Budget Guidance for Grants and Agreements OFFICE OF MANAGEMENT AND BUDGET GOVERNMENTWIDE GUIDANCE FOR GRANTS AND AGREEMENTS Reserved...

  16. Medical device data systems and FDA regulation. Should medical device data systems require FDA clearance?

    PubMed

    Kelley, Peter

    2010-01-01

    It is widely understood why medical devices need to be regulated by the FDA and other governing bodies. However medical software does not typically require the same level of regulation. Currently the FDA is investigating whether one type of medical software, Medical Device Data Systems (MDDS), should require FDA clearance because of the potential risk they impose when interconnected with medical devices. Hospitals are looking to implement MDDS because the technology allows nursing staff to spend more time on direct patient care and reduces charting errors. This article will explore the FDA's proposal and will review the possible risks and provide a rationale for why MDDS should be regulated by the FDA and why MDDS vendors should have the right level of quality and risk management procedures in place to ensure that they are developing and bringing to market the safest products possible. PMID:20677470

  17. Additional requirements for charitable hospitals; community health needs assessments for charitable hospitals; requirement of a section 4959 excise tax return and time for filing the return. Final regulations and removal of temporary regulations.

    PubMed

    2014-12-31

    This document contains final regulations that provide guidance regarding the requirements for charitable hospital organizations added by the Patient Protection and Affordable Care Act of 2010. The regulations will affect charitable hospital organizations PMID:25562896

  18. RCRA corrective action permit requirements and modifications under Subpart F regulations. RCRA Information Brief

    SciTech Connect

    Coalgate, J.

    1993-07-01

    The ground water protection requirements under the Resource Conservation and Recovery Act (RCRA), 40 CFR 264, Subpart F, apply to surface impoundments, waste plies, land treatment units, and landfills that received hazardous waste after July 26,1982 (i.e., regulated units). There are three phases to the Subpart F ground water protection requirements: detection monitoring, compliance monitoring, and corrective action. Subpart F corrective action applies to remediation of ground water contamination resulting from releases from regulated units at a treatment, storage, or disposal facility (TSDF). The TSDF owner or operator is responsible for complying with these requirements. This Information Brief provides information on the permit requirements under Subpart F. This Information Brief is one of a series on RCRA corrective action. The first step in the permitting process is for the facility to determine the need for ground-water monitoring. The regulations found in 40 CFR 264 Sections 264.90 to 264.100 (Subpart F) apply to all regulated units. A ``regulated unit`` is defined as a surface impoundment, waste pile, landfill, or land treatment unit that received hazardous waste after July 26, 1982. Such units require a permit under RCRA. Subpart F entails a three-phased program designed to detect, evaluate, and, if necessary, respond to ground water contamination. The ground-water protection standard, including identification of maximum contaminant levels (MCLs) under the Safe Drinking Water Act (SDWA) and alternate concentration limits (ACLs), is established with the permit application. Where MCLs and ACLs cannot be established, the standard may be established at background levels.

  19. Root growth regulation and gravitropism in maize roots does not require the epidermis

    NASA Technical Reports Server (NTRS)

    Bjorkman, T.; Cleland, R. E.

    1991-01-01

    We have earlier published observations showing that endogenous alterations in growth rate during gravitropism in maize roots (Zea mays L.) are unaffected by the orientation of cuts which remove epidermal and cortical tissue in the growing zone (Bjorkman and Cleland, 1988, Planta 176, 513-518). We concluded that the epidermis and cortex are not essential for transporting a growth-regulating signal in gravitropism or straight growth, nor for regulating the rate of tissue expansion. This conclusion has been challenged by Yang et al. (1990, Planta 180, 530-536), who contend that a shallow girdle around the entire perimeter of the root blocks gravitropic curvature and that this inhibition is the result of a requirement for epidermal cells to transport the growth-regulating signal. In this paper we demonstrate that the entire epidermis can be removed without blocking gravitropic curvature and show that the position of narrow girdles does not affect the location of curvature. We therefore conclude that the epidermis is not required for transport of a growth-regulating substance from the root cap to the growing zone, nor does it regulate the growth rate of the elongating zone of roots.

  20. Characterization of parameters required for effective use of tamoxifen-regulated recombination.

    PubMed

    Buelow, Ben; Scharenberg, Andrew M

    2008-01-01

    Conditional gene targeting using the Cre-loxp system is a well established technique in numerous in vitro and in vivo systems. Ligand regulated forms of Cre have been increasingly used in these applications in order to gain temporal and spatial control over conditional targeting. The tamoxifen-regulated Cre variant mer-Cre-mer (mCrem) is widely utilized because of its reputation for tight regulation in the absence of its tamoxifen ligand. In the DT40 chicken B cell line, we generated an mCrem-based reversible switch for conditional regulation of a transgene, and in contrast with previous work, observed significant constitutive activity of mCrem. This prompted us to use our system for analysis of the parameters governing tamoxifen-regulated mCrem recombination of a genomic target. We find that robust mCrem expression correlates with a high level of tamoxifen-independent Cre activity, while clones expressing mCrem at the limit of western blot detection exhibit extremely tight regulation. We also observe time and dose-dependent effects on mCrem activity which suggest limitations on the use of conditional targeting approaches for applications which require tight temporal coordination of Cre action within a cell population. PMID:18810268

  1. An essential single domain response regulator required for normal cell division and differentiation in Caulobacter crescentus.

    PubMed Central

    Hecht, G B; Lane, T; Ohta, N; Sommer, J M; Newton, A

    1995-01-01

    Signal transduction pathways mediated by sensor histidine kinases and cognate response regulators control a variety of physiological processes in response to environmental conditions. Here we show that in Caulobacter crescentus these systems also play essential roles in the regulation of polar morphogenesis and cell division. Previous studies have implicated histidine kinase genes pleC and divJ in the regulation of these developmental events. We now report that divK encodes an essential, cell cycle-regulated homolog of the CheY/Spo0F subfamily and present evidence that this protein is a cognate response regulator of the histidine kinase PleC. The purified kinase domain of PleC, like that of DivJ, can serve as an efficient phosphodonor to DivK and as a phospho-DivK phosphatase. Based on these and earlier genetic results we propose that PleC and DivK are members of a signal transduction pathway that couples motility and stalk formation to completion of a late cell division cycle event. Gene disruption experiments and the filamentous phenotype of the conditional divK341 mutant reveal that DivK also functions in an essential signal transduction pathway required for cell division, apparently in response to another histidine kinase. We suggest that phosphotransfer mediated by these two-component signal transduction systems may represent a general mechanism regulating cell differentiation and cell division in response to successive cell cycle checkpoints. Images PMID:7664732

  2. p73 Is Required for Multiciliogenesis and Regulates the Foxj1-Associated Gene Network.

    PubMed

    Marshall, Clayton B; Mays, Deborah J; Beeler, J Scott; Rosenbluth, Jennifer M; Boyd, Kelli L; Santos Guasch, Gabriela L; Shaver, Timothy M; Tang, Lucy J; Liu, Qi; Shyr, Yu; Venters, Bryan J; Magnuson, Mark A; Pietenpol, Jennifer A

    2016-03-15

    We report that p73 is expressed in multiciliated cells (MCCs), is required for MCC differentiation, and directly regulates transcriptional modulators of multiciliogenesis. Loss of ciliary biogenesis provides a unifying mechanism for many phenotypes observed in p73 knockout mice including hydrocephalus; hippocampal dysgenesis; sterility; and chronic inflammation/infection of lung, middle ear, and sinus. Through p73 and p63 ChIP-seq using murine tracheal cells, we identified over 100 putative p73 target genes that regulate MCC differentiation and homeostasis. We validated Foxj1, a transcriptional regulator of multiciliogenesis, and many other cilia-associated genes as direct target genes of p73 and p63. We show p73 and p63 are co-expressed in a subset of basal cells and suggest that p73 marks these cells for MCC differentiation. In summary, p73 is essential for MCC differentiation, functions as a critical regulator of a transcriptome required for MCC differentiation, and, like p63, has an essential role in development of tissues. PMID:26947080

  3. p73 is Required for Multiciliogenesis and Regulates the Foxj1-Associated Gene Network

    PubMed Central

    Marshall, Clayton B; Mays, Deborah J; Beeler, J Scott; Rosenbluth, Jennifer M; Boyd, Kelli L; Guasch, Gabriela L Santos; Shaver, Timothy M; Tang, Lucy J; Liu, Qi; Shyr, Yu; Venters, Bryan J; Magnuson, Mark A; Pietenpol, Jennifer A

    2016-01-01

    Summary We report that p73 is expressed in multiciliated cells (MCCs), is required for MCC differentiation, and directly regulates transcriptional modulators of multiciliogenesis. Loss of ciliary biogenesis provides a unifying mechanism for many phenotypes observed in p73 knockout mice including hydrocephalus, hippocampal dysgenesis, sterility and chronic inflammation/infection of lung, middle ear and sinus. Through p73 and p63 ChIP-seq using murine tracheal cells, we identified over 100 putative p73 target genes that regulate MCC differentiation and homeostasis. We validated Foxj1, a transcriptional regulator of multiciliogenesis, and many other cilia-associated genes as direct target genes of p73 and p63. We show p73 and p63 are co-expressed in a subset of basal cells, and suggest that p73 ‘marks’ these cells for MCC differentiation. In sum, p73 is essential for MCC differentiation, functions as a critical regulator of a transcriptome required for MCC differentiation and, like p63, has an essential role in development of tissues. PMID:26947080

  4. 33 CFR 165.830 - Regulated Navigation Area; Reporting Requirements for Barges Loaded with Certain Dangerous...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... regulations contained in 33 CFR 165.13 apply to this section. (e) Eighth Coast Guard District Inland River RNA...— Barge means a non-self propelled vessel engaged in commerce, as set out in 33 CFR 160.204. Certain... CFR 173.50. (2) Division 1.5D blasting agents for which a permit is required under 49 CFR 176.415...

  5. 33 CFR 165.830 - Regulated Navigation Area; Reporting Requirements for Barges Loaded with Certain Dangerous...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... regulations contained in 33 CFR 165.13 apply to this section. (e) Eighth Coast Guard District Inland River RNA...— Barge means a non-self propelled vessel engaged in commerce, as set out in 33 CFR 160.204. Certain... CFR 173.50. (2) Division 1.5D blasting agents for which a permit is required under 49 CFR 176.415...

  6. 33 CFR 165.830 - Regulated Navigation Area; Reporting Requirements for Barges Loaded with Certain Dangerous...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... regulations contained in 33 CFR 165.13 apply to this section. (e) Eighth Coast Guard District Inland River RNA...— Barge means a non-self propelled vessel engaged in commerce, as set out in 33 CFR 160.204. Certain... CFR 173.50. (2) Division 1.5D blasting agents for which a permit is required under 49 CFR 176.415...

  7. The Global Regulator CodY Regulates Toxin Gene Expression in Bacillus anthracis and Is Required for Full Virulence▿ †

    PubMed Central

    van Schaik, Willem; Château, Alice; Dillies, Marie-Agnès; Coppée, Jean-Yves; Sonenshein, Abraham L.; Fouet, Agnès

    2009-01-01

    In gram-positive bacteria, CodY is an important regulator of genes whose expression changes upon nutrient limitation and acts as a repressor of virulence gene expression in some pathogenic species. Here, we report the role of CodY in Bacillus anthracis, the etiologic agent of anthrax. Disruption of codY completely abolished virulence in a toxinogenic, noncapsulated strain, indicating that the activity of CodY is required for full virulence of B. anthracis. Global transcriptome analysis of a codY mutant and the parental strain revealed extensive differences. These differences could reflect direct control for some genes, as suggested by the presence of CodY binding sequences in their promoter regions, or indirect effects via the CodY-dependent control of other regulatory proteins or metabolic rearrangements in the codY mutant strain. The differences included reduced expression of the anthrax toxin genes in the mutant strain, which was confirmed by lacZ reporter fusions and immunoblotting. The accumulation of the global virulence regulator AtxA protein was strongly reduced in the mutant strain. However, in agreement with the microarray data, expression of atxA, as measured using an atxA-lacZ transcriptional fusion and by assaying atxA mRNA, was not significantly affected in the codY mutant. An atxA-lacZ translational fusion was also unaffected. Overexpression of atxA restored toxin component synthesis in the codY mutant strain. These results suggest that CodY controls toxin gene expression by regulating AtxA accumulation posttranslationally. PMID:19651859

  8. Using Five-Minute Data to Allocate Load-Following and Regulation Requirements among Individual Customers

    SciTech Connect

    Kirby, B.J.

    2001-03-27

    B. Kirby and E. Hirst, Customer-Specific Metrics for the Regulation and Load-Following 1 Ancillary Services, ORNL/CON-474, Oak Ridge National Laboratory, Oak Ridge, Tenn., January 2000. In an earlier project, we analyzed data on total system load and the loads of eight large industrial customers in terms of system- and customer-specific requirements for the regulation and load-following ancillary services. We conducted these analyses using 12 days of data from February 1 1999 plus 12 days of data from August and September 1999. These analyses were conducted using data provided by the control area at the 30-s level, which we then aggregated to the 2-min level for subsequent analysis. The current project analyzes the feasibility of using 5-min revenue-meter (RM) data to allocate load-following and regulation requirements among retail customers. This project does not use the 5-min data to determine the actual ancillary services requirements for individual loads because these requirements depend strongly on the time-averaging period chosen for the load data. In particular, the amount of regulation required declines as the time-averaging period increases. Our earlier project showed that 2 min was a reasonable time-averaging period for this control area. The reason for examining 5-min data is that supervisory control and data acquisition (SCADA) data, which are available every 4 s, are collected for only eight of this control area's very largest industrial customers. On the other hand, this control area collects 5-min RM data for about 600 customers. Although these customers account for less than 0.2% of the retail customers, they account for 60% of total energy sales and more than 40% of total revenues. Thus, if the allocations obtained with 5-min data for these eight large customers agree well with the allocations obtained with the SCADA data for these customers, the method we developed to allocate regulation costs to individual customers can be applied to many more

  9. Sterol homeostasis requires regulated degradation of squalene monooxygenase by the ubiquitin ligase Doa10/Teb4

    PubMed Central

    Foresti, Ombretta; Ruggiano, Annamaria; Hannibal-Bach, Hans K; Ejsing, Christer S; Carvalho, Pedro

    2013-01-01

    Sterol homeostasis is essential for the function of cellular membranes and requires feedback inhibition of HMGR, a rate-limiting enzyme of the mevalonate pathway. As HMGR acts at the beginning of the pathway, its regulation affects the synthesis of sterols and of other essential mevalonate-derived metabolites, such as ubiquinone or dolichol. Here, we describe a novel, evolutionarily conserved feedback system operating at a sterol-specific step of the mevalonate pathway. This involves the sterol-dependent degradation of squalene monooxygenase mediated by the yeast Doa10 or mammalian Teb4, a ubiquitin ligase implicated in a branch of the endoplasmic reticulum (ER)-associated protein degradation (ERAD) pathway. Since the other branch of ERAD is required for HMGR regulation, our results reveal a fundamental role for ERAD in sterol homeostasis, with the two branches of this pathway acting together to control sterol biosynthesis at different levels and thereby allowing independent regulation of multiple products of the mevalonate pathway. DOI: http://dx.doi.org/10.7554/eLife.00953.001 PMID:23898401

  10. IL-12 is required for mTOR regulation of memory CTLs during viral infection

    PubMed Central

    Garcia, Karla; Sun, Zhifeng; Mattson, Elliot; Li, Lei; Smyth, Kendra; Xiao, Zhengguo

    2014-01-01

    The induction of functional memory CTLs is a major goal of vaccination against intracellular pathogens. IL-12 is critical for the generation of memory CTLs, and inhibition of mTOR by rapamycin can effectively enhance the memory CTL response. Yet, the role of IL-12 in mTOR’s regulation of memory CTL is unknown. Here, we hypothesized that the immunostimulatory effects of mTOR on memory CTLs requires IL-12 signaling. Our results revealed that rapamycin increased the generation of memory CTLs in vaccinia virus infection, and this enhancement was dependent upon the IL-12 signal. Furthermore, IL-12 receptor deficiency diminished the secondary expansion of rapamycin-regulated memory, and resultant secondary memory CTLs were abolished. Rapamycin enhanced IL-12 signaling by up regulating IL-12 receptor β2 expression and STAT4 phosphorylation in CTLs during early infection. In addition, rapamycin continually suppressed T-bet expression in both WT and IL-12 receptor knockout CTLs. These results indicate an essential role for IL-12 in the regulation of memory CTLs by mTOR, and highlight the importance of considering the interplay between cytokines and adjuvants during vaccine design. PMID:24898389

  11. TMEM203 Is a Novel Regulator of Intracellular Calcium Homeostasis and Is Required for Spermatogenesis

    PubMed Central

    Shambharkar, Prashant B.; Bittinger, Mark; Latario, Brian; Xiong, ZhaoHui; Bandyopadhyay, Somnath; Davis, Vanessa; Lin, Victor; Yang, Yi; Valdez, Reginald; Labow, Mark A.

    2015-01-01

    Intracellular calcium signaling is critical for initiating and sustaining diverse cellular functions including transcription, synaptic signaling, muscle contraction, apoptosis and fertilization. Trans-membrane 203 (TMEM203) was identified here in cDNA overexpression screens for proteins capable of modulating intracellular calcium levels using activation of a calcium/calcineurin regulated transcription factor as an indicator. Overexpression of TMEM203 resulted in a reduction of Endoplasmic Reticulum (ER) calcium stores and elevation in basal cytoplasmic calcium levels. TMEM203 protein was localized to the ER and found associated with a number of ER proteins which regulate ER calcium entry and efflux. Mouse Embryonic Fibroblasts (MEFs) derived from Tmem203 deficient mice had reduced ER calcium stores and altered calcium homeostasis. Tmem203 deficient mice were viable though male knockout mice were infertile and exhibited a severe block in spermiogenesis and spermiation. Expression profiling studies showed significant alternations in expression of calcium channels and pumps in testes and concurrently Tmem203 deficient spermatocytes demonstrated significantly altered calcium handling. Thus Tmem203 is an evolutionarily conserved regulator of cellular calcium homeostasis, is required for spermatogenesis and provides a causal link between intracellular calcium regulation and spermiogenesis. PMID:25996873

  12. Neto2 is a KCC2 interacting protein required for neuronal Cl− regulation in hippocampal neurons

    PubMed Central

    Ivakine, Evgueni A.; Acton, Brooke A.; Mahadevan, Vivek; Ormond, Jake; Tang, Man; Pressey, Jessica C.; Huang, Michelle Y.; Ng, David; Delpire, Eric; Salter, Michael W.; Woodin, Melanie A.; McInnes, Roderick R.

    2013-01-01

    KCC2 is a neuron-specific K+–Cl− cotransporter that is essential for Cl− homeostasis and fast inhibitory synaptic transmission in the mature CNS. Despite the critical role of KCC2 in neurons, the mechanisms regulating its function are not understood. Here, we show that KCC2 is critically regulated by the single-pass transmembrane protein neuropilin and tolloid like-2 (Neto2). Neto2 is required to maintain the normal abundance of KCC2 and specifically associates with the active oligomeric form of the transporter. Loss of the Neto2:KCC2 interaction reduced KCC2-mediated Cl− extrusion, resulting in decreased synaptic inhibition in hippocampal neurons. PMID:23401525

  13. FOXO signaling is required for disuse muscle atrophy and is directly regulated by Hsp70

    PubMed Central

    Senf, Sarah M.; Dodd, Stephen L.

    2010-01-01

    The purpose of the current study was to determine whether heat shock protein 70 (Hsp70) directly regulates forkhead box O (FOXO) signaling in skeletal muscle. This aim stems from previous work demonstrating that Hsp70 overexpression inhibits disuse-induced FOXO transactivation and prevents muscle fiber atrophy. However, although FOXO is sufficient to cause muscle wasting, no data currently exist on the requirement of FOXO signaling in the progression of physiological muscle wasting, in vivo. In the current study we show that specific inhibition of FOXO, via expression of a dominant-negative FOXO3a, in rat soleus muscle during disuse prevented >40% of muscle fiber atrophy, demonstrating that FOXO signaling is required for disuse muscle atrophy. Subsequent experiments determined whether Hsp70 directly regulates FOXO3a signaling when independently activated in skeletal muscle, via transfection of FOXO3a. We show that Hsp70 inhibits FOXO3a-dependent transcription in a gene-specific manner. Specifically, Hsp70 inhibited FOXO3a-induced promoter activation of atrogin-1, but not MuRF1. Further studies showed that a FOXO3a DNA-binding mutant can activate MuRF1, but not atrogin-1, suggesting that FOXO3a activates these two genes through differential mechanisms. In summary, FOXO signaling is required for physiological muscle atrophy and is directly inhibited by Hsp70. PMID:19864323

  14. Unusually long-lived pause required for regulation of a Rho-dependent transcription terminator

    PubMed Central

    Hollands, Kerry; Sevostiyanova, Anastasia; Groisman, Eduardo A.

    2014-01-01

    Up to half of all transcription termination events in bacteria rely on the RNA-dependent helicase Rho. However, the nucleic acid sequences that promote Rho-dependent termination remain poorly characterized. Defining the molecular determinants that confer Rho-dependent termination is especially important for understanding how such terminators can be regulated in response to specific signals. Here, we identify an extraordinarily long-lived pause at the site where Rho terminates transcription in the 5′-leader region of the Mg2+ transporter gene mgtA in Salmonella enterica. We dissect the sequence elements required for prolonged pausing in the mgtA leader and establish that the remarkable longevity of this pause is required for a riboswitch to stimulate Rho-dependent termination in the mgtA leader region in response to Mg2+ availability. Unlike Rho-dependent terminators described previously, where termination occurs at multiple pause sites, there is a single site of transcription termination directed by Rho in the mgtA leader. Our data suggest that Rho-dependent termination events that are subject to regulation may require elements distinct from those operating at constitutive Rho-dependent terminators. PMID:24778260

  15. Smad4 is required to regulate the fate of cranial neural crest cells

    PubMed Central

    Ko, Seung O; Chung, Il Hyuk; Xu, Xun; Oka, Shoji; Zhao, Hu; Cho, Eui Sic; Deng, Chuxia; Chai, Yang

    2009-01-01

    Smad4 is the central mediator for TGF-β/BMP signals, which are involved in regulating cranial neural crest (CNC) cell formation, migration, proliferation and fate determination. It is unclear whether TGF-β/BMP signals utilize Smad-dependent or –independent pathways to control the development of CNC cells. To investigate the functional significance of Smad4 in regulating CNC cells, we generated mice with neural crest specific inactivation of the Smad4 gene. Our study shows that Smad4 is not required for the migration of CNC cells, but is required in neural crest cells for the development of the cardiac outflow tract. Smad4 is essential in mediating BMP signaling in the CNC-derived ectomesenchyme during early stages of tooth development because conditional inactivation of Smad4 in neural crest derived cells results in incisor and molar development arrested at the dental lamina stage. Furthermore, Smad-mediated TGF-β/BMP signaling controls the homeobox gene patterning of oral/aboral and proximal/distal domains within the first branchial arch. At the cellular level, a Smad4-mediated downstream target gene(s) is required for the survival of CNC cells in the proximal domain of the first branchial arch. Smad4 mutant mice show underdevelopment of the first branchial arch and midline fusion defects. Taken together, our data show that TGF-β/BMP signals rely on Smad-dependent pathways in the ectomesenchyme to mediate epithelial-mesenchymal interactions that control craniofacial organogenesis. PMID:17964566

  16. 75 FR 45104 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-02

    ... Regulation Supplement; Administrative Matters AGENCY: Defense Acquisition Regulations System, Department of... Federal Acquisition Regulation Supplement (DFARS) Part 204, Administrative Matters, and related clauses...

  17. 76 FR 72916 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-28

    ... Regulation Supplement; Administrative Matters AGENCY: Defense Acquisition Regulations System, Department of... Acquisition Regulation Supplement (DFARS) Part 204, Administrative Matters: U.S. International Atomic...

  18. 76 FR 35424 - Information Collection Requirements; Defense Federal Acquisition Regulation Supplement...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-17

    ... Regulation Supplement; Construction and Architect-Engineer Contracts AGENCY: Defense Acquisition Regulations... Acquisition Regulation Supplement (DFARS) Part 236, Construction and Architect-Engineer Contracts, and...

  19. Plasma membrane H+-ATPase regulation is required for auxin gradient formation preceding phototropic growth

    PubMed Central

    Hohm, Tim; Demarsy, Emilie; Quan, Clément; Allenbach Petrolati, Laure; Preuten, Tobias; Vernoux, Teva; Bergmann, Sven; Fankhauser, Christian

    2014-01-01

    Phototropism is a growth response allowing plants to align their photosynthetic organs toward incoming light and thereby to optimize photosynthetic activity. Formation of a lateral gradient of the phytohormone auxin is a key step to trigger asymmetric growth of the shoot leading to phototropic reorientation. To identify important regulators of auxin gradient formation, we developed an auxin flux model that enabled us to test in silico the impact of different morphological and biophysical parameters on gradient formation, including the contribution of the extracellular space (cell wall) or apoplast. Our model indicates that cell size, cell distributions, and apoplast thickness are all important factors affecting gradient formation. Among all tested variables, regulation of apoplastic pH was the most important to enable the formation of a lateral auxin gradient. To test this prediction, we interfered with the activity of plasma membrane H+-ATPases that are required to control apoplastic pH. Our results show that H+-ATPases are indeed important for the establishment of a lateral auxin gradient and phototropism. Moreover, we show that during phototropism, H+-ATPase activity is regulated by the phototropin photoreceptors, providing a mechanism by which light influences apoplastic pH. PMID:25261457

  20. Endocytosis-dependent coordination of multiple actin regulators is required for wound healing

    PubMed Central

    Matsubayashi, Yutaka; Coulson-Gilmer, Camilla

    2015-01-01

    The ability to heal wounds efficiently is essential for life. After wounding of an epithelium, the cells bordering the wound form dynamic actin protrusions and/or a contractile actomyosin cable, and these actin structures drive wound closure. Despite their importance in wound healing, the molecular mechanisms that regulate the assembly of these actin structures at wound edges are not well understood. In this paper, using Drosophila melanogaster embryos, we demonstrate that Diaphanous, SCAR, and WASp play distinct but overlapping roles in regulating actin assembly during wound healing. Moreover, we show that endocytosis is essential for wound edge actin assembly and wound closure. We identify adherens junctions (AJs) as a key target of endocytosis during wound healing and propose that endocytic remodeling of AJs is required to form “signaling centers” along the wound edge that control actin assembly. We conclude that coordination of actin assembly, AJ remodeling, and membrane traffic is required for the construction of a motile leading edge during wound healing. PMID:26216900

  1. Hic-5 is required for myofibroblast differentiation by regulating mechanically dependent MRTF-A nuclear accumulation.

    PubMed

    Varney, Scott D; Betts, Courtney B; Zheng, Rui; Wu, Lei; Hinz, Boris; Zhou, Jiliang; Van De Water, Livingston

    2016-02-15

    How mechanical cues from the extracellular environment are translated biochemically to modulate the effects of TGF-β on myofibroblast differentiation remains a crucial area of investigation. We report here that the focal adhesion protein, Hic-5 (also known as TGFB1I1), is required for the mechanically dependent generation of stress fibers in response to TGF-β. Successful generation of stress fibers promotes the nuclear localization of the transcriptional co-factor MRTF-A (also known as MKL1), and this correlates with the mechanically dependent induction of α smooth muscle actin (α-SMA) and Hic-5 in response to TGF-β. As a consequence of regulating stress fiber assembly, Hic-5 is required for the nuclear accumulation of MRTF-A and the induction of α-SMA as well as cellular contractility, suggesting a crucial role for Hic-5 in myofibroblast differentiation. Indeed, the expression of Hic-5 was transient in acute wounds and persistent in pathogenic scars, and Hic-5 colocalized with α-SMA expression in vivo. Taken together, these data suggest that a mechanically dependent feed-forward loop, elaborated by the reciprocal regulation of MRTF-A localization by Hic-5 and Hic-5 expression by MRTF-A, plays a crucial role in myofibroblast differentiation in response to TGF-β. PMID:26759173

  2. Extracellular Matrix-Regulated Gene Expression RequiresCooperation of SWI/SNF and Transcription Factors

    SciTech Connect

    Xu, Ren; Spencer, Virginia A.; Bissell, Mina J.

    2006-05-25

    Extracellular cues play crucial roles in the transcriptional regulation of tissue-specific genes, but whether and how these signals lead to chromatin remodeling is not understood and subject to debate. Using chromatin immunoprecipitation (ChIP) assays and mammary-specific genes as models, we show here that extracellular matrix (ECM) molecules and prolactin cooperate to induce histone acetylation and binding of transcription factors and the SWI/SNF complex to the {beta}- and ?-casein promoters. Introduction of a dominant negative Brg1, an ATPase subunit of SWI/SNF complex, significantly reduced both {beta}- and ?-casein expression, suggesting that SWI/SNF-dependent chromatin remodeling is required for transcription of mammary-specific genes. ChIP analyses demonstrated that the ATPase activity of SWI/SNF is necessary for recruitment of RNA transcriptional machinery, but not for binding of transcription factors or for histone acetylation. Coimmunoprecipitation analyses showed that the SWI/SNF complex is associated with STAT5, C/EBP{beta}, and glucocorticoid receptor (GR). Thus, ECM- and prolactin-regulated transcription of the mammary-specific casein genes requires the concerted action of chromatin remodeling enzymes and transcription factors.

  3. TNL-mediated immunity in Arabidopsis requires complex regulation of the redundant ADR1 gene family.

    PubMed

    Dong, Oliver Xiaoou; Tong, Meixuezi; Bonardi, Vera; El Kasmi, Farid; Woloshen, Virginia; Wünsch, Lisa K; Dangl, Jeffery L; Li, Xin

    2016-05-01

    Nucleotide-binding leucine-rich repeat proteins (NLRs) serve as intracellular immune receptors in animals and plants. Sensor NLRs perceive pathogen-derived effector molecules and trigger robust host defense. Recent studies revealed the role of three coiled-coil-type NLRs (CNLs) of the ADR1 family - ADR1, ADR1-L1 and ADR1-L2 - as redundant helper NLRs, whose function is required for defense mediated by multiple sensor NLRs. From a mutant snc1-enhancing (MUSE) forward genetic screen in Arabidopsis targeted to identify negative regulators of snc1 that encodes a TIR-type NLR (TNL), we isolated two alleles of muse15, both carrying mutations in ADR1-L1. Interestingly, loss of ADR1-L1 also enhances immunity-related phenotypes in other autoimmune mutants including cpr1, bal and lsd1. This immunity-enhancing effect is not mediated by increased SNC1 protein stability, nor is it fully dependent on the accumulation of the defense hormone salicylic acid (SA). Transcriptional analysis revealed an upregulation of ADR1 and ADR1-L2 in the adr1-L1 background, which may overcompensate the loss of ADR1-L1, resulting in enhanced immunity. Interestingly, autoimmunity of snc1 and chs2, which encode typical TNLs, is fully suppressed by the adr1 triple mutant, suggesting that the ADRs are required for TNL downstream signaling. This study extends our knowledge on the interplay among ADRs and reveals their complexity in defense regulation. PMID:27074399

  4. Proper gibberellin localization in vascular tissue is required to regulate adventitious root development in tobacco.

    PubMed

    Niu, Shihui; Li, Zhexin; Yuan, Huwei; Fang, Pan; Chen, Xiaoyang; Li, Wei

    2013-08-01

    Bioactive gibberellins (GAs) are involved in many developmental aspects of the life cycle of plants, acting either directly or through interaction with other hormones. Accumulating evidence suggests that GAs have an important effect on root growth; however, there is currently little information on the specific regulatory mechanism of GAs during adventitious root development. A study was conducted on tobacco (Nicotiana tabacum) plants for altered rates of biosynthesis, catabolism, and GA signalling constitutively or in specific tissues using a transgenic approach. In the present study, PtGA20ox, PtGA2ox1, and PtGAI were overexpressed under the control of the 35S promoter, vascular cambium-specific promoter (LMX5), or root meristem-specific promoter (TobRB7), respectively. Evidence is provided that the precise localization of bioactive GA in the stem but not in the roots is required to regulate adventitious root development in tobacco. High levels of GA negatively regulate the early initiation step of root formation through interactions with auxin, while a proper and mobile GA signal is required for the emergence and subsequent long-term elongation of established primordia. The results demonstrated that GAs have an inhibitory effect on adventitious root formation but a stimulatory effect on root elongation. PMID:23918971

  5. Acinetobacter baumannii Response to Host-Mediated Zinc Limitation Requires the Transcriptional Regulator Zur

    PubMed Central

    Mortensen, Brittany L.; Rathi, Subodh; Chazin, Walter J.

    2014-01-01

    Acinetobacter baumannii is a leading cause of ventilator-associated pneumonia in intensive care units, and the increasing rates of antibiotic resistance make treating these infections challenging. Consequently, there is an urgent need to develop new antimicrobials to treat A. baumannii infections. One potential therapeutic option is to target bacterial systems involved in maintaining appropriate metal homeostasis, processes that are critical for the growth of pathogens within the host. The A. baumannii inner membrane zinc transporter ZnuABC is required for growth under low-zinc conditions and for A. baumannii pathogenesis. The expression of znuABC is regulated by the transcriptional repressor Zur. To investigate the role of Zur during the A. baumannii response to zinc limitation, a zur deletion mutant was generated, and transcriptional changes were analyzed using RNA sequencing. A number of Zur-regulated genes were identified that exhibit increased expression both when zur is absent and under low-zinc conditions, and Zur binds to predicted Zur box sequences of several genes affected by zinc levels or the zur mutation. Furthermore, the zur mutant is impaired for growth in the presence of both high and low zinc levels compared to wild-type A. baumannii. Finally, the zur mutant exhibits a defect in dissemination in a mouse model of A. baumannii pneumonia, establishing zinc sensing as a critical process during A. baumannii infection. These results define Zur-regulated genes within A. baumannii and demonstrate a requirement for Zur in the A. baumannii response to the various zinc levels experienced within the vertebrate host. PMID:24816603

  6. UHRF1 regulation of Dnmt1 is required for pre-gastrula zebrafish development

    PubMed Central

    Kent, Brandon; Magnani, Elena; Walsh, Martin J.; Sadler, Kirsten C.

    2016-01-01

    Landmark epigenetic events underlie early embryonic development, yet how epigenetic modifiers are regulated to achieve rapid epigenome re-patterning is not known. Uhrf1 and DNA methyltransferase 1 (Dnmt1) are known to largely mediate maintenance DNA methylation and Uhrf1 is also required for both Dnmt1 localization and stability. Here, we investigate how these two key epigenetic modifiers regulate early zebrafish development and characterize the developmental consequences of disrupting their homeostatic relationship. Unlike Uhrf1 knockdown, which causes developmental arrest and death prior to gastrulation, overexpression of human UHRF1 (WT-UHRF1) caused asymmetric epiboly, inefficient gastrulation and multi-systemic defects. UHRF1 phosphorylation was previously demonstrated as essential for zebrafish embryogenesis, and we found that penetrance of the asymmetric epiboly phenotype was significantly increased in embryos injected with mRNA encoding non-phosphorylatable UHRF1 (UHRF1S661A). Surprisingly, both WT-UHRF1 and UHRF1S661A overexpression caused DNA hypomethylation. However, since other approaches that caused an equivalent degree of DNA hypomethylation did not cause the asymmetric epiboly phenotype, we conclude that bulk DNA methylation is not the primary mechanism. Instead, UHRF1S661A overexpression resulted in accumulation of Dnmt1 protein and the overexpression of both WT and a catalytically inactive Dnmt1 phenocopied the WT-UHRF1 overexpressing embryos. Dnmt1 knockdown suppressed the phenotype caused by UHRF1S661A overexpression, and Uhrf1 knockdown suppressed the effect of Dnmt1 overexpression. Therefore, we conclude that the interaction between these two proteins is the mechanism underlying the observed developmental defects. This indicates that Dnmt1 stability requires UHRF1 phosphorylation and that crosstalk between the proteins is essential for the function of these two important epigenetic regulators during gastrulation. PMID:26851214

  7. Telomere Length Regulation and Telomeric Chromatin Require the Nonsense-Mediated mRNA Decay Pathway

    PubMed Central

    Lew, Jodi E.; Enomoto, Shinichiro; Berman, Judith

    1998-01-01

    Rap1p localization factor 4 (RLF4) is a Saccharomyces cerevisiae gene that was identified in a screen for mutants that affect telomere function and alter the localization of the telomere binding protein Rap1p. In rlf4 mutants, telomeric silencing is reduced and telomere DNA tracts are shorter, indicating that RLF4 is required for both the establishment and/or maintenance of telomeric chromatin and for the control of telomere length. In this paper, we demonstrate that RLF4 is allelic to NMD2/UPF2, a gene required for the nonsense-mediated mRNA decay (NMD) pathway (Y. Cui, K. W. Hagan, S. Zhang, and S. W. Peltz, Mol. Cell. Biol. 9:423–436, 1995, and F. He and A. Jacobson, Genes Dev. 9:437–454, 1995). The NMD pathway, which requires Nmd2p/Rlf4p together with two other proteins, (Upf1p and Upf3p), targets nonsense messages for degradation in the cytoplasm by the exoribonuclease Xrn1p. Deletion of UPF1 and UPF3 caused telomere-associated defects like those caused by rlf4 mutations, implying that the NMD pathway, rather than an NMD-independent function of Nmd2p/Rlf4p, is required for telomere functions. In addition, telomere length regulation required Xrn1p but not Rat1p, a nuclear exoribonuclease with functional similarity to Xrn1p (A. W. Johnson, Mol. Cell. Biol. 17:6122–6130, 1997). In contrast, telomere-associated defects were not observed in pan2, pan3, or pan2 pan3 strains, which are defective in the intrinsic deadenylation-dependent decay of normal (as opposed to nonsense) mRNAs. Thus, loss of the NMD pathway specifically causes defects at telomeres, demonstrating a physiological requirement for the NMD pathway in normal cell functions. We propose a model in which the NMD pathway regulates the levels of specific mRNAs that are important for telomere functions. PMID:9742129

  8. 43 CFR 1821.12 - Are these the only regulations that will apply to my application or other required document?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Are these the only regulations that will apply to my application or other required document? 1821.12 Section 1821.12 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR GENERAL MANAGEMENT (1000) APPLICATION...

  9. 43 CFR 1821.12 - Are these the only regulations that will apply to my application or other required document?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Are these the only regulations that will apply to my application or other required document? 1821.12 Section 1821.12 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR...

  10. 7 CFR 301.76-4 - Labeling requirements for regulated nursery stock produced within an area quarantined for citrus...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... produced within an area quarantined for citrus greening. 301.76-4 Section 301.76-4 Agriculture Regulations... OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Citrus Greening and Asian Citrus Psyllid § 301.76-4 Labeling requirements for regulated nursery stock produced within an area quarantined for citrus...

  11. 7 CFR 301.76-4 - Labeling requirements for regulated nursery stock produced within an area quarantined for citrus...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... produced within an area quarantined for citrus greening. 301.76-4 Section 301.76-4 Agriculture Regulations... OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Citrus Greening and Asian Citrus Psyllid § 301.76-4 Labeling requirements for regulated nursery stock produced within an area quarantined for citrus...

  12. 7 CFR 301.76-4 - Labeling requirements for regulated nursery stock produced within an area quarantined for citrus...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... produced within an area quarantined for citrus greening. 301.76-4 Section 301.76-4 Agriculture Regulations... OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Citrus Greening and Asian Citrus Psyllid § 301.76-4 Labeling requirements for regulated nursery stock produced within an area quarantined for citrus...

  13. Transcriptional regulation via nuclear receptor crosstalk required for the Drosophila circadian clock.

    PubMed

    Jaumouillé, Edouard; Machado Almeida, Pedro; Stähli, Patrick; Koch, Rafael; Nagoshi, Emi

    2015-06-01

    Circadian clocks in large part rely on transcriptional feedback loops. At the core of the clock machinery, the transcriptional activators CLOCK/BMAL1 (in mammals) and CLOCK/CYCLE (CLK/CYC) (in Drosophila) drive the expression of the period (per) family genes. The PER-containing complexes inhibit the activity of CLOCK/BMAL1 or CLK/CYC, thereby forming a negative feedback loop [1]. In mammals, the ROR and REV-ERB family nuclear receptors add positive and negative transcriptional regulation to this core negative feedback loop to ensure the generation of robust circadian molecular oscillation [2]. Despite the overall similarities between mammalian and Drosophila clocks, whether comparable mechanisms via nuclear receptors are required for the Drosophila clock remains unknown. We show here that the nuclear receptor E75, the fly homolog of REV-ERB α and REV-ERB β, and the NR2E3 subfamily nuclear receptor UNF are components of the molecular clocks in the Drosophila pacemaker neurons. In vivo assays in conjunction with the in vitro experiments demonstrate that E75 and UNF bind to per regulatory sequences and act together to enhance the CLK/CYC-mediated transcription of the per gene, thereby completing the core transcriptional feedback loop necessary for the free-running clockwork. Our results identify a missing link in the Drosophila clock and highlight the significance of the transcriptional regulation via nuclear receptors in metazoan circadian clocks. PMID:26004759

  14. Abl Kinases Regulate HGF/Met Signaling Required for Epithelial Cell Scattering, Tubulogenesis and Motility

    PubMed Central

    Li, Ran; Knight, Jennifer F.; Park, Morag; Pendergast, Ann Marie

    2015-01-01

    Tight regulation of receptor tyrosine kinases (RTKs) is crucial for normal development and homeostasis. Dysregulation of RTKs signaling is associated with diverse pathological conditions including cancer. The Met RTK is the receptor for hepatocyte growth factor (HGF) and is dysregulated in numerous human tumors. Here we show that Abl family of non-receptor tyrosine kinases, comprised of Abl (ABL1) and Arg (ABL2), are activated downstream of the Met receptor, and that inhibition of Abl kinases dramatically suppresses HGF-induced cell scattering and tubulogenesis. We uncover a critical role for Abl kinases in the regulation of HGF/Met-dependent RhoA activation and RhoA-mediated actomyosin contractility and actin cytoskeleton remodeling in epithelial cells. Moreover, treatment of breast cancer cells with Abl inhibitors markedly decreases Met-driven cell migration and invasion. Notably, expression of a transforming mutant of the Met receptor in the mouse mammary epithelium results in hyper-activation of both Abl and Arg kinases. Together these data demonstrate that Abl kinases link Met activation to Rho signaling and Abl kinases are required for Met-dependent cell scattering, tubulogenesis, migration, and invasion. Thus, inhibition of Abl kinases might be exploited for the treatment of cancers driven by hyperactivation of HGF/Met signaling. PMID:25946048

  15. Nuclear-localized CTP:phosphocholine cytidylyltransferase α regulates phosphatidylcholine synthesis required for lipid droplet biogenesis

    PubMed Central

    Aitchison, Adam J.; Arsenault, Daniel J.; Ridgway, Neale D.

    2015-01-01

    The reversible association of CTP:phosphocholine cytidylyltransferase α (CCTα) with membranes regulates the synthesis of phosphatidylcholine (PC) by the CDP-choline (Kennedy) pathway. Based on results with insect CCT homologues, translocation of nuclear CCTα onto cytoplasmic lipid droplets (LDs) is proposed to stimulate the synthesis of PC that is required for LD biogenesis and triacylglycerol (TAG) storage. We examined whether this regulatory mechanism applied to LD biogenesis in mammalian cells. During 3T3-L1 and human preadipocyte differentiation, CCTα expression and PC synthesis was induced. In 3T3-L1 cells, CCTα translocated from the nucleoplasm to the nuclear envelope and cytosol but did not associate with LDs. The enzyme also remained in the nucleus during human adipocyte differentiation. RNAi silencing in 3T3-L1 cells showed that CCTα regulated LD size but did not affect TAG storage or adipogenesis. LD biogenesis in nonadipocyte cell lines treated with oleate also promoted CCTα translocation to the nuclear envelope and/or cytoplasm but not LDs. In rat intestinal epithelial cells, CCTα silencing increased LD size, but LD number and TAG deposition were decreased due to oleate-induced cytotoxicity. We conclude that CCTα increases PC synthesis for LD biogenesis by translocation to the nuclear envelope and not cytoplasmic LDs. PMID:26108622

  16. Transcriptional Regulation via Nuclear Receptor Crosstalk Required for the Drosophila Circadian Clock

    PubMed Central

    Jaumouillé, Edouard; Machado Almeida, Pedro; Stähli, Patrick; Koch, Rafael; Nagoshi, Emi

    2015-01-01

    Summary Circadian clocks in large part rely on transcriptional feedback loops. At the core of the clock machinery, the transcriptional activators CLOCK/BMAL1 (in mammals) and CLOCK/CYCLE (CLK/CYC) (in Drosophila) drive the expression of the period (per) family genes. The PER-containing complexes inhibit the activity of CLOCK/BMAL1 or CLK/CYC, thereby forming a negative feedback loop [1]. In mammals, the ROR and REV-ERB family nuclear receptors add positive and negative transcriptional regulation to this core negative feedback loop to ensure the generation of robust circadian molecular oscillation [2]. Despite the overall similarities between mammalian and Drosophila clocks, whether comparable mechanisms via nuclear receptors are required for the Drosophila clock remains unknown. We show here that the nuclear receptor E75, the fly homolog of REV-ERB α and REV-ERB β, and the NR2E3 subfamily nuclear receptor UNF are components of the molecular clocks in the Drosophila pacemaker neurons. In vivo assays in conjunction with the in vitro experiments demonstrate that E75 and UNF bind to per regulatory sequences and act together to enhance the CLK/CYC-mediated transcription of the per gene, thereby completing the core transcriptional feedback loop necessary for the free-running clockwork. Our results identify a missing link in the Drosophila clock and highlight the significance of the transcriptional regulation via nuclear receptors in metazoan circadian clocks. PMID:26004759

  17. DNA sequence-specific recognition by a transcriptional regulator requires indirect readout of A-tracts

    PubMed Central

    Mendieta, Jesús; Pérez-Lago, Laura; Salas, Margarita; Camacho, Ana

    2007-01-01

    The bacteriophage Ø29 transcriptional regulator p4 binds to promoters of different intrinsic activities. The p4–DNA complex contains two identical protomers that make similar interactions with the target sequence 5′-AACTTTTT-15 bp-AAAATGTT-3′. To define how the various elements in the target sequence contribute to p4's affinity, we studied p4 binding to a series of mutated binding sites. The binding specificity depends critically on base pairs of the target sequence through both direct as well as indirect readout. There is only one specific contact between a base and an amino acid residue; other contacts take place with the phosphate backbone. Alteration of direct amino acid–base contacts, or mutation of non-contacted A·T base pairs at A-tracts abolished binding. We generated three 5 ns molecular dynamics (MD) simulations to investigate the basis for the p4–DNA complex specificity. Recognition is controlled by the protein and depends on DNA dynamic properties. MD results on protein–DNA contacts and the divergence of p4 affinity to modified binding sites reveal an inherent asymmetry, which is required for p4-specific binding and may be crucial for transcription regulation. PMID:17452358

  18. Learned stressor resistance requires extracellular signal-regulated kinase in the prefrontal cortex

    PubMed Central

    Christianson, John P.; Flyer-Adams, Johanna G.; Drugan, Robert C.; Amat, Jose; Daut, Rachel A.; Foilb, Allison R.; Watkins, Linda R.; Maier, Steven F.

    2014-01-01

    Behaviorally controllable stressors confer protection from the neurochemical and behavioral consequences of future uncontrollable stressors, a phenomenon termed “behavioral immunization”. Recent data implicate protein synthesis within the ventromedial prefrontal cortex (mPFC) as critical to behavioral immunization. Adult, male Sprague-Dawley rats were exposed to a series of controllable tailshocks and 1 week later to uncontrollable tailshocks, followed 24 h later by social exploration and shuttlebox escape tests. To test the involvement of N-methyl-D-aspartate receptors (NMDARs) and the extracellular signal-regulated kinase (ERK) cascade in behavioral immunization, either D-AP5 or the MEK inhibitor U0126 was injected to the prelimbic (PL) or infralimbic (IL) mPFC prior to controllable stress exposure. Phosphorylated ERK and P70S6K, regulators of transcription and translation, were quantified by Western blot or immunohistochemistry after controllable or uncontrollable tailshocks. Prior controllable stress prevented the social exploration and shuttlebox performance deficits caused by the later uncontrollable stressor, and this effect was blocked by injections of D-AP5 into mPFC. A significant increase in phosphorylated ERK1 and ERK2, but not P70S6K, occurred within the PL and IL in rats exposed to controllable stress, but not to uncontrollable stress. However, U0126 only prevented behavioral immunization when injected to the PL. We provide evidence that NMDAR and ERK dependent signaling within the PL region is required for behavioral immunization, a learned form of stressor resistance. PMID:25324750

  19. 78 FR 70294 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-25

    ... Regulation Supplement; Administrative Matters AGENCY: Defense Acquisition Regulations System, Department of..., Administrative Matters, and related clauses at DFARS 252.204; DD Form 2051, Request for Assignment of...

  20. 75 FR 47561 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Contract...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-06

    ... Regulation Supplement; Contract Financing (OMB Control Number 0704- 0359) AGENCY: Defense Acquisition... and OMB Number: Defense Federal Acquisition Regulation Supplement (DFARS) part 232, Contract...

  1. The splicing regulator Rbfox2 is required for both cerebellar development and mature motor function

    PubMed Central

    Gehman, Lauren T.; Meera, Pratap; Stoilov, Peter; Shiue, Lily; O'Brien, Janelle E.; Meisler, Miriam H.; Ares, Manuel; Otis, Thomas S.; Black, Douglas L.

    2012-01-01

    The Rbfox proteins (Rbfox1, Rbfox2, and Rbfox3) regulate the alternative splicing of many important neuronal transcripts and have been implicated in a variety of neurological disorders. However, their roles in brain development and function are not well understood, in part due to redundancy in their activities. Here we show that, unlike Rbfox1 deletion, the CNS-specific deletion of Rbfox2 disrupts cerebellar development. Genome-wide analysis of Rbfox2−/− brain RNA identifies numerous splicing changes altering proteins important both for brain development and mature neuronal function. To separate developmental defects from alterations in the physiology of mature cells, Rbfox1 and Rbfox2 were deleted from mature Purkinje cells, resulting in highly irregular firing. Notably, the Scn8a mRNA encoding the Nav1.6 sodium channel, a key mediator of Purkinje cell pacemaking, is improperly spliced in RbFox2 and Rbfox1 mutant brains, leading to highly reduced protein expression. Thus, Rbfox2 protein controls a post-transcriptional program required for proper brain development. Rbfox2 is subsequently required with Rbfox1 to maintain mature neuronal physiology, specifically Purkinje cell pacemaking, through their shared control of sodium channel transcript splicing. PMID:22357600

  2. The splicing regulator Rbfox2 is required for both cerebellar development and mature motor function.

    PubMed

    Gehman, Lauren T; Meera, Pratap; Stoilov, Peter; Shiue, Lily; O'Brien, Janelle E; Meisler, Miriam H; Ares, Manuel; Otis, Thomas S; Black, Douglas L

    2012-03-01

    The Rbfox proteins (Rbfox1, Rbfox2, and Rbfox3) regulate the alternative splicing of many important neuronal transcripts and have been implicated in a variety of neurological disorders. However, their roles in brain development and function are not well understood, in part due to redundancy in their activities. Here we show that, unlike Rbfox1 deletion, the CNS-specific deletion of Rbfox2 disrupts cerebellar development. Genome-wide analysis of Rbfox2(-/-) brain RNA identifies numerous splicing changes altering proteins important both for brain development and mature neuronal function. To separate developmental defects from alterations in the physiology of mature cells, Rbfox1 and Rbfox2 were deleted from mature Purkinje cells, resulting in highly irregular firing. Notably, the Scn8a mRNA encoding the Na(v)1.6 sodium channel, a key mediator of Purkinje cell pacemaking, is improperly spliced in RbFox2 and Rbfox1 mutant brains, leading to highly reduced protein expression. Thus, Rbfox2 protein controls a post-transcriptional program required for proper brain development. Rbfox2 is subsequently required with Rbfox1 to maintain mature neuronal physiology, specifically Purkinje cell pacemaking, through their shared control of sodium channel transcript splicing. PMID:22357600

  3. Sequence Requirements for Myosin Gene Expression and Regulation in Caenorhabditis Elegans

    PubMed Central

    Okkema, P. G.; Harrison, S. W.; Plunger, V.; Aryana, A.; Fire, A.

    1993-01-01

    Four Caenorhabditis elegans genes encode muscle-type specific myosin heavy chain isoforms: myo-1 and myo-2 are expressed in the pharyngeal muscles; unc-54 and myo-3 are expressed in body wall muscles. We have used transformation-rescue and lacZ fusion assays to determine sequence requirements for regulated myosin gene expression during development. Multiple tissue-specific activation elements are present for all four genes. For each of the four genes, sequences upstream of the coding region are tissue-specific promoters, as shown by their ability to drive expression of a reporter gene (lacZ) in the appropriate muscle type. Each gene contains at least one additional tissue-specific regulatory element, as defined by the ability to enhance expression of a heterologous promoter in the appropriate muscle type. In rescue experiments with unc-54, two further requirements apparently independent of tissue specificity were found: sequences within the 3' non-coding region are essential for activity while an intron near the 5' end augments expression levels. The general intron stimulation is apparently independent of intron sequence, indicating a mechanistic effect of splicing. To further characterize the myosin gene promoters and to examine the types of enhancer sequences in the genome, we have initiated a screen of C. elegans genomic DNA for fragments capable of enhancing the myo-2 promoter. The properties of enhancers recovered from this screen suggest that the promoter is limited to muscle cells in its ability to respond to enhancers. PMID:8244003

  4. Nutritional requirements and nitrogen-dependent regulation of proteinase activity of Lactobacillus helveticus CRL 1062.

    PubMed

    Hebert, E M; Raya, R R; De Giori, G S

    2000-12-01

    The nutritional requirements of Lactobacillus helveticus CRL 1062 were determined with a simplified chemically defined medium (SCDM) and compared with those of L. helveticus CRL 974 (ATCC 15009). Both strains were found to be prototrophic for alanine, glycine, asparagine, glutamine, and cysteine. In addition, CRL 1062 also showed prototrophy for lysine and serine. The microorganisms also required riboflavin, calcium pantothenate, pyridoxal, nicotinic acid, and uracil for growth in liquid SCDM. The growth rate and the synthesis of their cell membrane-bound serine proteinases, but not of their intracellular leucyl-aminopeptidases, were influenced by the peptide content of the medium. The highest proteinase levels were found during cell growth in basal SCDM, while the synthesis of this enzyme was inhibited in SCDM supplemented with Casitone, Casamino Acids, or beta-casein. Low-molecular-mass peptides (<3,000 Da), extracted from Casitone, and the dipeptide leucylproline (final concentration, 5 mM) play important roles in the medium-dependent regulation of proteinase activity. The addition of the dipeptide leucylproline (5 mM) to SCDM reduced proteinase activity by 25%. PMID:11097908

  5. Arabidopsis PROTEASOME REGULATOR1 is required for auxin-mediated suppression of proteasome activity and regulates auxin signalling.

    PubMed

    Yang, Bao-Jun; Han, Xin-Xin; Yin, Lin-Lin; Xing, Mei-Qing; Xu, Zhi-Hong; Xue, Hong-Wei

    2016-01-01

    The plant hormone auxin is perceived by the nuclear F-box protein TIR1 receptor family and regulates gene expression through degradation of Aux/IAA transcriptional repressors. Several studies have revealed the importance of the proteasome in auxin signalling, but details on how the proteolytic machinery is regulated and how this relates to degradation of Aux/IAA proteins remains unclear. Here we show that an Arabidopsis homologue of the proteasome inhibitor PI31, which we name PROTEASOME REGULATOR1 (PTRE1), is a positive regulator of the 26S proteasome. Loss-of-function ptre1 mutants are insensitive to auxin-mediated suppression of proteasome activity, show diminished auxin-induced degradation of Aux/IAA proteins and display auxin-related phenotypes. We found that auxin alters the subcellular localization of PTRE1, suggesting this may be part of the mechanism by which it reduces proteasome activity. Based on these results, we propose that auxin regulates proteasome activity via PTRE1 to fine-tune the homoeostasis of Aux/IAA repressor proteins thus modifying auxin activity. PMID:27109828

  6. Arabidopsis PROTEASOME REGULATOR1 is required for auxin-mediated suppression of proteasome activity and regulates auxin signalling

    PubMed Central

    Yang, Bao-Jun; Han, Xin-Xin; Yin, Lin-Lin; Xing, Mei-Qing; Xu, Zhi-Hong; Xue, Hong-Wei

    2016-01-01

    The plant hormone auxin is perceived by the nuclear F-box protein TIR1 receptor family and regulates gene expression through degradation of Aux/IAA transcriptional repressors. Several studies have revealed the importance of the proteasome in auxin signalling, but details on how the proteolytic machinery is regulated and how this relates to degradation of Aux/IAA proteins remains unclear. Here we show that an Arabidopsis homologue of the proteasome inhibitor PI31, which we name PROTEASOME REGULATOR1 (PTRE1), is a positive regulator of the 26S proteasome. Loss-of-function ptre1 mutants are insensitive to auxin-mediated suppression of proteasome activity, show diminished auxin-induced degradation of Aux/IAA proteins and display auxin-related phenotypes. We found that auxin alters the subcellular localization of PTRE1, suggesting this may be part of the mechanism by which it reduces proteasome activity. Based on these results, we propose that auxin regulates proteasome activity via PTRE1 to fine-tune the homoeostasis of Aux/IAA repressor proteins thus modifying auxin activity. PMID:27109828

  7. Temporal requirements of the fragile X mental retardation protein in the regulation of synaptic structure.

    PubMed

    Gatto, Cheryl L; Broadie, Kendal

    2008-08-01

    Fragile X syndrome (FraX), caused by the loss-of-function of one gene (FMR1), is the most common inherited form of both mental retardation and autism spectrum disorders. The FMR1 product (FMRP) is an mRNA-binding translation regulator that mediates activity-dependent control of synaptic structure and function. To develop any FraX intervention strategy, it is essential to define when and where FMRP loss causes the manifestation of synaptic defects, and whether the reintroduction of FMRP can restore normal synapse properties. In the Drosophila FraX model, dFMRP loss causes neuromuscular junction (NMJ) synapse over-elaboration (overgrowth, overbranching, excess synaptic boutons), accumulation of development-arrested satellite boutons, and altered neurotransmission. We used the Gene-Switch method to conditionally drive dFMRP expression to define the spatiotemporal requirements in synaptic mechanisms. Constitutive induction of targeted neuronal dFMRP at wild-type levels rescues all synaptic architectural defects in Drosophila Fmr1 (dfmr1)-null mutants, demonstrating a presynaptic requirement for synapse structuring. By contrast, presynaptic dFMRP expression does not ameliorate functional neurotransmission defects, indicating a postsynaptic dFMRP requirement. Strikingly, targeted early induction of dFMRP effects nearly complete rescue of synaptic structure defects, showing a primarily early-development role. In addition, acute dFMRP expression at maturity partially alleviates dfmr1-null defects, although rescue is not as complete as either early or constitutive dFMRP expression, showing a modest capacity for late-stage structural plasticity. We conclude that dFMRP predominantly acts early in synaptogenesis to modulate architecture, but that late dFMRP introduction at maturity can weakly compensate for early absence of dFMRP function. PMID:18579676

  8. Temporal Requirements of the Fragile X Mental Retardation Protein in the Regulation of Synaptic Structure

    PubMed Central

    Gatto, Cheryl L.; Broadie, Kendal

    2009-01-01

    Fragile X Syndrome (FraX), caused by the loss of function of one gene (FMR1), is the most common inherited form of both mental retardation and autism spectrum disorders. The FMR1 product (FMRP) is an mRNA-binding translation regulator that mediates activity-dependent control of synaptic structure and function. To develop any FraX intervention strategy, it is critical to define when and where FMRP loss causes the manifestation of synaptic defects, and whether reintroduction of FMRP can restore normal synapse properties. In the Drosophila FraX model, dFMRP loss causes neuromuscular junction (NMJ) synapse over-elaboration (overgrowth, overbranching, excess synaptic boutons), accumulation of development-arrested satellite boutons, and altered neurotransmission. We have used the Gene-Switch (GS) method to conditionally drive dFMRP to define the spatiotemporal requirements in synaptic mechanisms. Constitutive induction of targeted neuronal dFMRP at wild-type levels rescues all synaptic architectural defects in dfmr1 null mutants, demonstrating a presynaptic requirement for synapse structuring. In contrast, presynaptic dFMRP expression does not ameliorate functional neurotransmission defects, indicating a postsynaptic dFMRP requirement. Strikingly, targeted early induction of dFMRP effects nearly complete rescue of synaptic structure defects, showing a primarily early development role. In addition, acute dFMRP expression at maturity partially alleviates dfmr1 null defects, although rescue is not as complete as either early or constitutive dFMRP expression, showing a modest capacity for late-stage structural plasticity. We conclude that dFMRP predominantly acts early in synaptogenesis to modulate architecture, but that late dFMRP introduction at maturity can weakly compensate for early absence of dFMRP function. PMID:18579676

  9. Profiles of Motivated Self-Regulation in College Computer Science Courses: Differences in Major versus Required Non-Major Courses

    ERIC Educational Resources Information Center

    Shell, Duane F.; Soh, Leen-Kiat

    2013-01-01

    The goal of the present study was to utilize a profiling approach to understand differences in motivation and strategic self-regulation among post-secondary STEM students in major versus required non-major computer science courses. Participants were 233 students from required introductory computer science courses (194 men; 35 women; 4 unknown) at…

  10. 76 FR 36905 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Taxes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-23

    ... Regulation Supplement; Taxes AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD... Supplement (DFARS) Part 229, Taxes, and related clause at DFARS 252.229-7010; OMB Control Number...

  11. 76 FR 67152 - Federal Acquisition Regulation; Submission for OMB Review; Cost or Pricing Data Requirements and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-31

    ... in the Federal Register at 76 FR 35218, on June 16, 2011. No comments were received. Public comments... Pricing Data, by any of the following methods: Regulations.gov : http://www.regulations.gov . Sub...

  12. Requirement for non-regulated, constitutive calcium influx in macrophage survival signaling

    SciTech Connect

    Tano, Jean-Yves; Vazquez, Guillermo

    2011-04-08

    Highlights: {yields} We examine the role of constitutive Ca{sup 2+} influx in macrophage survival. {yields} Survival signaling exhibits a mandatory requirement for constitutive Ca{sup 2+} influx. {yields} CAM/CAMKII couples constitutive Ca{sup 2+} influx to survival signaling. -- Abstract: The phosphatidylinositol-3-kinase (PI3K)/AKT axis and the Nuclear Factor kappa B (NF{kappa}B) pathway play critical roles in macrophage survival. In cells other than macrophages proper operation of those two pathways requires Ca{sup 2+} influx into the cell, but if that is the case in macrophages remains unexplored. In the present work we used THP-1-derived macrophages and a pharmacological approach to examine for the first time the role of constitutive, non-regulated Ca{sup 2+} influx in PI3K/AKT and NF{kappa}B signaling. Blocking constitutive function of Ca{sup 2+}-permeable channels with the organic channel blocker SKF96365 completely prevented phosphorylation of I{kappa}B{alpha}, AKT and its downstream target BAD in TNF{alpha}-treated macrophages. A similar effect was observed upon treating macrophages with the calmodulin (CAM) inhibitor W-7 or the calmodulin-dependent kinase II (CAMKII) inhibitor KN-62. In addition, pre-treating macrophages with SKF96365 significantly enhanced TNF{alpha}-induced apoptosis. Our findings suggest that in THP-1-derived macrophages survival signaling depends, to a significant extent, on constitutive Ca{sup 2+} influx presumably through a mechanism that involves the CAM/CAMKII axis as a coupling component between constitutive Ca{sup 2+} influx and activation of survival signaling.

  13. 77 FR 58817 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement (DFARS...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-24

    ... Regulation Supplement (DFARS); Contract Financing AGENCY: Defense Acquisition Regulations System, Department... comments. Email: dfars@osd.mil . Include OMB Control Number 0704-0321 in the subject line of the message..., Associated Form, and OMB Number: Defense Federal Acquisition Regulation Supplement (DFARS) Part 232,...

  14. 78 FR 68829 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Contract...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-15

    ... Regulation Supplement; Contract Financing AGENCY: Defense Acquisition Regulations System, Department of.... Email: dfars@osd.mil . Include OMB Control Number 0704-0359 in the subject line of the message. Fax... Federal Acquisition Regulation Supplement (DFARS) Part 232, Contract Financing, and related clause...

  15. Retinophilin is a light-regulated phosphoprotein required to suppress photoreceptor dark noise in Drosophila

    PubMed Central

    Mecklenburg, Kirk L.; Takemori, Nobuaki; Komori, Naoka; Chu, Brian; Hardie, Roger C.; Matsumoto, Hiroyuki; O’Tousa, Joseph. E.

    2010-01-01

    Photoreceptor cells achieve high sensitivity, reliably detecting single photons, while limiting the spontaneous activation events responsible for dark noise. We used proteomic, genetic, and electrophysiological approaches to characterize Retinophilin (RTP/CG10233) in Drosophila photoreceptors, and establish its involvement in dark noise suppression. RTP possesses MORN (Membrane Occupation and Recognition Nexus) motifs, a structure shared with mammalian junctophilins and other membrane-associated proteins found within excitable cells. We show the MORN repeats, and both the N- and C-terminal domains, are required for RTP localization in the microvillar light gathering organelle, the rhabdomere. RTP exists in multiple phosphorylated isoforms under dark conditions and is dephosphorylated by light exposure. An RTP deletion mutant exhibits a high rate of spontaneous membrane depolarization events in dark conditions but retains the normal kinetics of the light response. Photoreceptors lacking NINAC myosin III, a motor protein/kinase, also display a similar dark noise phenotype as the RTP deletion. We show that NINAC mutants are depleted for RTP. These results suggest the increase in dark noise in NINAC mutants is due to lack of RTP, and further, defines a novel role for NINAC in the rhabdomere. We propose that RTP is a light-regulated phosphoprotein that organizes rhabdomeric components to suppress random activation of the phototransduction cascade and thus increases the signaling fidelity of dark-adapted photoreceptors. PMID:20107052

  16. The Second Subunit of DNA Polymerase Delta Is Required for Genomic Stability and Epigenetic Regulation.

    PubMed

    Zhang, Jixiang; Xie, Shaojun; Cheng, Jinkui; Lai, Jinsheng; Zhu, Jian-Kang; Gong, Zhizhong

    2016-06-01

    DNA polymerase δ plays crucial roles in DNA repair and replication as well as maintaining genomic stability. However, the function of POLD2, the second small subunit of DNA polymerase δ, has not been characterized yet in Arabidopsis (Arabidopsis thaliana). During a genetic screen for release of transcriptional gene silencing, we identified a mutation in POLD2. Whole-genome bisulfite sequencing indicated that POLD2 is not involved in the regulation of DNA methylation. POLD2 genetically interacts with Ataxia Telangiectasia-mutated and Rad3-related and DNA polymerase α The pold2-1 mutant exhibits genomic instability with a high frequency of homologous recombination. It also exhibits hypersensitivity to DNA-damaging reagents and short telomere length. Whole-genome chromatin immunoprecipitation sequencing and RNA sequencing analyses suggest that pold2-1 changes H3K27me3 and H3K4me3 modifications, and these changes are correlated with the gene expression levels. Our study suggests that POLD2 is required for maintaining genome integrity and properly establishing the epigenetic markers during DNA replication to modulate gene expression. PMID:27208288

  17. Multiple protein kinase A-regulated events are required for transcriptional induction by cAMP.

    PubMed Central

    Brindle, P; Nakajima, T; Montminy, M

    1995-01-01

    The second messenger cAMP stimulates the expression of numerous genes via the protein kinase A-mediated phosphorylation of the cAMP response element-binding protein (CREB) at Ser-133. Ser-133 phosphorylation, in turn, appears to induce target gene expression by promoting interaction between CREB and CBP, a 265-kDa nuclear phospho-CREB-binding protein. It is unclear, however, whether Ser-133 phosphorylation per se is sufficient for CREB-CBP complex formation and for target gene induction in vivo. Here we examine CREB activity in Jurkat T cells after stimulation of the T-cell receptor (TCR), an event that leads to calcium entry and diacylglycerol production. Triggering of the TCR stimulated Ser-133 phosphorylation of CREB with high stoichiometry, but TCR activation did not promote CREB-CBP complex formation or target gene induction unless suboptimal doses of cAMP agonist were provided as a costimulus. Our results demonstrate that, in addition to mediating Ser-133 phosphorylation of CREB, protein kinase A regulates additional proteins that are required for recruitment of the transcriptional apparatus to cAMP-responsive genes. Images Fig. 1 Fig. 2 Fig. 3 PMID:7479832

  18. MT1-MMP is required for myeloid cell fusion via regulation of Rac1 signaling

    PubMed Central

    Gonzalo, Pilar; Guadamillas, Marta C.; Hernández-Riquer, Mª Victoria; Pollán, Ángela; Grande-García, Araceli; Bartolomé, Rubén A.; Vasanji, Amit; Ambrogio, Chiara; Chiarle, Roberto; Teixidó, Joaquín; Risteli, Juha; Apte, Suneel S.; del Pozo, Miguel A.; Arroyo, Alicia G.

    2009-01-01

    SUMMARY Cell fusion is essential for fertilization, myotube formation, and inflammation. Macrophages fuse in various circumstances but the molecular signals involved in the distinct steps of their fusion are not fully characterized. Using null mice and derived cells, we show that the protease MT1-MMP is necessary for macrophage fusion during osteoclast and giant cell formation in vitro and in vivo. Specifically, MT1-MMP is required for lamellipodia formation and for proper cell morphology and motility of bone marrow myeloid progenitors prior to membrane fusion. These functions of MT1-MMP do not depend on MT1-MMP catalytic activity or downstream pro-MMP-2 activation. Instead, MT1-MMP-null cells show a decreased Rac1 activity and reduced membrane targeting of Rac1 and the adaptor protein p130Cas. Retroviral rescue experiments and protein binding assays delineate a signaling pathway in which MT1-MMP, via its cytosolic tail, contributes to macrophage migration and fusion by regulating Rac1 activity through an association with p130Cas. PMID:20152179

  19. Brg1 directly regulates Olig2 transcription and is required for oligodendrocyte progenitor cell specification.

    PubMed

    Matsumoto, Steven; Banine, Fatima; Feistel, Kerstin; Foster, Scott; Xing, Rubing; Struve, Jaime; Sherman, Larry S

    2016-05-15

    The Olig2 basic-helix-loop-helix transcription factor promotes oligodendrocyte specification in early neural progenitor cells (NPCs), including radial glial cells, in part by recruiting SWI/SNF chromatin remodeling complexes to the enhancers of genes involved in oligodendrocyte differentiation. How Olig2 expression is regulated during oligodendrogliogenesis is not clear. Here, we find that the Brg1 subunit of SWI/SNF complexes interacts with a proximal Olig2 promoter and represses Olig2 transcription in the mouse cortex at E14, when oligodendrocyte progenitors (OPCs) are not yet found in this location. Brg1 does not interact with the Olig2 promoter in the E14 ganglionic eminence, where NPCs differentiate into Olig2-positive OPCs. Consistent with these findings, Brg1-null NPCs demonstrate precocious expression of Olig2 in the cortex. However, these cells fail to differentiate into OPCs. We further find that Brg1 is necessary for neuroepithelial-to-radial glial cell transition, but not neuronal differentiation despite a reduction in expression of the pro-neural transcription factor Pax6. Collectively, these and earlier findings support a model whereby Brg1 promotes neurogenic radial glial progenitor cell specification but is dispensable for neuronal differentiation. Concurrently, Brg1 represses Olig2 expression and the specification of OPCs, but is required for OPC differentiation and oligodendrocyte maturation. PMID:27067865

  20. Novel insights into iron regulation and requirement in marine medaka Oryzias melastigma

    PubMed Central

    Wang, Jian; Wang, Wen-Xiong

    2016-01-01

    Iron (Fe) is an essential trace element for marine fish. However, our knowledge of Fe requirements at different development stages of marine fish is still limited. Here, we reported the efficient Fe absorption strategies adopted by larval fish under different dietary Fe supplementary levels (i.e., 0–640 mg/kg). Biokinetically, the larval fish controlled their dietary Fe assimilation efficiency (AE, 1.6–18.5%), and enhanced their waterborne Fe uptake (ca. 2.5 fold change of uptake rate constant) once the dietary Fe was deficient (i.e., 27.4 mg Fe/kg feed). Transcriptionally, the expression of hepcidin1 (hep1; Fe regulator; i.e., 2.3–15.7 fold change) in larval fish was positively correlated with the Fe supplementary levels. Comparatively, the female adult fish were poor in assimilating the added Fe source (i.e., ferric form) with similar life-sustainable levels of Fe (i.e., 0.046–0.12 μg/g/d assimilated for Fe supplementary levels of 27.4, 162 and 657 mg Fe/kg feed). The overall feeding experiments suggested that dietary net Fe flux sufficient for the normal growth of larval medaka was 0.71–1.75 μg/g/d (i.e., 83.9 mg Fe/kg feed), consistent with the modeled value (i.e., 1.09–2.16 μg/g/d). In female adults, the estimated essential net Fe flux was 0.88–0.90 μg/g/d. PMID:27216705

  1. Novel insights into iron regulation and requirement in marine medaka Oryzias melastigma.

    PubMed

    Wang, Jian; Wang, Wen-Xiong

    2016-01-01

    Iron (Fe) is an essential trace element for marine fish. However, our knowledge of Fe requirements at different development stages of marine fish is still limited. Here, we reported the efficient Fe absorption strategies adopted by larval fish under different dietary Fe supplementary levels (i.e., 0-640 mg/kg). Biokinetically, the larval fish controlled their dietary Fe assimilation efficiency (AE, 1.6-18.5%), and enhanced their waterborne Fe uptake (ca. 2.5 fold change of uptake rate constant) once the dietary Fe was deficient (i.e., 27.4 mg Fe/kg feed). Transcriptionally, the expression of hepcidin1 (hep1; Fe regulator; i.e., 2.3-15.7 fold change) in larval fish was positively correlated with the Fe supplementary levels. Comparatively, the female adult fish were poor in assimilating the added Fe source (i.e., ferric form) with similar life-sustainable levels of Fe (i.e., 0.046-0.12 μg/g/d assimilated for Fe supplementary levels of 27.4, 162 and 657 mg Fe/kg feed). The overall feeding experiments suggested that dietary net Fe flux sufficient for the normal growth of larval medaka was 0.71-1.75 μg/g/d (i.e., 83.9 mg Fe/kg feed), consistent with the modeled value (i.e., 1.09-2.16 μg/g/d). In female adults, the estimated essential net Fe flux was 0.88-0.90 μg/g/d. PMID:27216705

  2. Novel insights into iron regulation and requirement in marine medaka Oryzias melastigma

    NASA Astrophysics Data System (ADS)

    Wang, Jian; Wang, Wen-Xiong

    2016-05-01

    Iron (Fe) is an essential trace element for marine fish. However, our knowledge of Fe requirements at different development stages of marine fish is still limited. Here, we reported the efficient Fe absorption strategies adopted by larval fish under different dietary Fe supplementary levels (i.e., 0–640 mg/kg). Biokinetically, the larval fish controlled their dietary Fe assimilation efficiency (AE, 1.6–18.5%), and enhanced their waterborne Fe uptake (ca. 2.5 fold change of uptake rate constant) once the dietary Fe was deficient (i.e., 27.4 mg Fe/kg feed). Transcriptionally, the expression of hepcidin1 (hep1; Fe regulator; i.e., 2.3–15.7 fold change) in larval fish was positively correlated with the Fe supplementary levels. Comparatively, the female adult fish were poor in assimilating the added Fe source (i.e., ferric form) with similar life-sustainable levels of Fe (i.e., 0.046–0.12 μg/g/d assimilated for Fe supplementary levels of 27.4, 162 and 657 mg Fe/kg feed). The overall feeding experiments suggested that dietary net Fe flux sufficient for the normal growth of larval medaka was 0.71–1.75 μg/g/d (i.e., 83.9 mg Fe/kg feed), consistent with the modeled value (i.e., 1.09–2.16 μg/g/d). In female adults, the estimated essential net Fe flux was 0.88–0.90 μg/g/d.

  3. NFAT5 regulates the canonical Wnt pathway and is required for cardiomyogenic differentiation

    SciTech Connect

    Adachi, Atsuo; Takahashi, Tomosaburo; Ogata, Takehiro; Imoto-Tsubakimoto, Hiroko; Nakanishi, Naohiko; Ueyama, Tomomi; Matsubara, Hiroaki

    2012-09-28

    Highlights: Black-Right-Pointing-Pointer NFAT5 protein expression is downregulated during cardiomyogenesis. Black-Right-Pointing-Pointer Inhibition of NFAT5 function suppresses canonical Wnt signaling. Black-Right-Pointing-Pointer Inhibition of NFAT5 function attenuates mesodermal induction. Black-Right-Pointing-Pointer NFAT5 function is required for cardiomyogenesis. -- Abstract: While nuclear factor of activated T cells 5 (NFAT5), a transcription factor implicated in osmotic stress response, is suggested to be involved in other processes such as migration and proliferation, its role in cardiomyogenesis is largely unknown. Here, we examined the role of NFAT5 in cardiac differentiation of P19CL6 cells, and observed that it was abundantly expressed in undifferentiated P19CL6 cells, and its protein expression was significantly downregulated by enhanced proteasomal degradation during DMSO-induced cardiomyogenesis. Expression of a dominant negative mutant of NFAT5 markedly attenuated cardiomyogenesis, which was associated with the inhibition of mesodermal differentiation. TOPflash reporter assay revealed that the transcriptional activity of canonical Wnt signaling was activated prior to mesodermal differentiation, and this activation was markedly attenuated by NFAT5 inhibition. Pharmacological activation of canonical Wnt signaling by [2 Prime Z, 3 Prime E]-6-bromoindirubin-3 Prime -oxime (BIO) restored Brachyury expression in NFAT5DN-expressing cells. Inhibition of NFAT5 markedly attenuated Wnt3 and Wnt3a induction. Expression of Dkk1 and Cerberus1, which are secreted Wnt antagonists, was also inhibited by NFAT5 inhibition. Thus, endogenous NFAT5 regulates the coordinated expression of Wnt ligands and antagonists, which are essential for cardiomyogenesis through the canonical Wnt pathway. These results demonstrated a novel role of NFAT5 in cardiac differentiation of stem cells.

  4. Identification of domains required for developmentally regulated SNARE function in Saccharomyces cerevisiae.

    PubMed Central

    Neiman, A M; Katz, L; Brennwald, P J

    2000-01-01

    Saccharomyces cerevisiae cells contain two homologues of the mammalian t-SNARE protein SNAP-25, encoded by the SEC9 and SPO20 genes. Although both gene products participate in post-Golgi vesicle fusion events, they cannot substitute for one another; Sec9p is active primarily in vegetative cells while Spo20p functions only during sporulation. We have investigated the basis for the developmental stage-specific differences in the function of these two proteins. Localization of the other plasma membrane SNARE subunits, Ssop and Sncp, in sporulating cells suggests that these proteins act in conjunction with Spo20p in the formation of the prospore membrane. In vitro binding studies demonstrate that, like Sec9p, Spo20p binds specifically to the t-SNARE Sso1p and, once bound to Sso1p, can complex with the v-SNARE Snc2p. Therefore, Sec9p and Spo20p interact with the same binding partners, but developmental conditions appear to favor the assembly of complexes with Spo20p in sporulating cells. Analysis of chimeric Sec9p/Spo20p molecules indicates that regions in both the SNAP-25 domain and the unique N terminus of Spo20p are required for activity during sporulation. Additionally, the N terminus of Spo20p is inhibitory in vegetative cells. Deletion studies indicate that activation and inhibition are separable functions of the Spo20p N terminus. Our results reveal an additional layer of regulation of the SNARE complex, which is necessary only in sporulating cells. PMID:10924463

  5. 25 CFR 518.7 - If a tribe holds a certificate of self-regulation, is it required to report information to the...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 2 2012-04-01 2012-04-01 false If a tribe holds a certificate of self-regulation, is it... REGULATION OF CLASS II GAMING § 518.7 If a tribe holds a certificate of self-regulation, is it required to... certificate of self-regulation shall be required to submit a self-regulation report annually to the...

  6. 25 CFR 518.7 - If a tribe holds a certificate of self-regulation, is it required to report information to the...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 2 2013-04-01 2013-04-01 false If a tribe holds a certificate of self-regulation, is it... REGULATION OF CLASS II GAMING § 518.7 If a tribe holds a certificate of self-regulation, is it required to... certificate of self-regulation shall be required to submit a self-regulation report annually to the...

  7. 25 CFR 518.7 - If a tribe holds a certificate of self-regulation, is it required to report information to the...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 2 2011-04-01 2011-04-01 false If a tribe holds a certificate of self-regulation, is it... REGULATION OF CLASS II GAMING § 518.7 If a tribe holds a certificate of self-regulation, is it required to... certificate of self-regulation shall be required to submit a self-regulation report annually to the...

  8. 75 FR 26165 - Regulation of Fuels and Fuel Additives: Alternative Affirmative Defense Requirements for Ultra...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-11

    ...EPA is issuing a proposed rule to amend the diesel sulfur regulations to allow refiners, importers, distributors, and retailers of highway diesel fuel the option to use an alternative affirmative defense if the Agency finds highway diesel fuel samples above the specified sulfur standard at retail facilities. This rule also proposes to amend the gasoline benzene regulations to allow......

  9. 78 FR 67132 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Contract...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-08

    ... Regulation Supplement; Contract Pricing AGENCY: Defense Acquisition Regulations System, Department of Defense... comments. Email: dfars@osd.mil . Include OMB Control Number 0704-0232 in the subject line of the message...) Subpart 215.4, Contract Pricing; DD Form 1861, Contract Facilities Capital Cost of Money; OMB...

  10. 7 CFR 330.200 - Movement of plant pests regulated; permits required.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FEDERAL PLANT PEST REGULATIONS; GENERAL; PLANT PESTS; SOIL, STONE, AND QUARRY PRODUCTS; GARBAGE Movement of Plant Pests § 330.200 Movement of... 7 Agriculture 5 2014-01-01 2014-01-01 false Movement of plant pests regulated; permits...

  11. 7 CFR 330.200 - Movement of plant pests regulated; permits required.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FEDERAL PLANT PEST REGULATIONS; GENERAL; PLANT PESTS; SOIL, STONE, AND QUARRY PRODUCTS; GARBAGE Movement of Plant Pests § 330.200 Movement of... 7 Agriculture 5 2013-01-01 2013-01-01 false Movement of plant pests regulated; permits...

  12. 7 CFR 330.200 - Movement of plant pests regulated; permits required.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FEDERAL PLANT PEST REGULATIONS; GENERAL; PLANT PESTS; SOIL, STONE, AND QUARRY PRODUCTS; GARBAGE Movement of Plant Pests § 330.200 Movement of... 7 Agriculture 5 2011-01-01 2011-01-01 false Movement of plant pests regulated; permits...

  13. 7 CFR 330.200 - Movement of plant pests regulated; permits required.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FEDERAL PLANT PEST REGULATIONS; GENERAL; PLANT PESTS; SOIL, STONE, AND QUARRY PRODUCTS; GARBAGE Movement of Plant Pests § 330.200 Movement of... 7 Agriculture 5 2012-01-01 2012-01-01 false Movement of plant pests regulated; permits...

  14. 7 CFR 330.200 - Movement of plant pests regulated; permits required.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FEDERAL PLANT PEST REGULATIONS; GENERAL; PLANT PESTS; SOIL, STONE, AND QUARRY PRODUCTS; GARBAGE Movement of Plant Pests § 330.200 Movement of... 7 Agriculture 5 2010-01-01 2010-01-01 false Movement of plant pests regulated; permits...

  15. 78 FR 30898 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Rights in...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-23

    ... Regulation Supplement; Rights in Technical Data and Computer Software AGENCY: Defense Acquisition Regulations... in Technical Data, and Subpart 227.72, Rights in Computer Software and Computer Software... are associated with rights in technical data and computer software. DoD needs this information...

  16. Five Conditions Commonly Used to Down-regulate Tor Complex 1 Generate Different Physiological Situations Exhibiting Distinct Requirements and Outcomes*

    PubMed Central

    Tate, Jennifer J.; Cooper, Terrance G.

    2013-01-01

    Five different physiological conditions have been used interchangeably to establish the sequence of molecular events needed to achieve nitrogen-responsive down-regulation of TorC1 and its subsequent regulation of downstream reporters: nitrogen starvation, methionine sulfoximine (Msx) addition, nitrogen limitation, rapamycin addition, and leucine starvation. Therefore, we tested a specific underlying assumption upon which the interpretation of data generated by these five experimental perturbations is premised. It is that they generate physiologically equivalent outcomes with respect to TorC1, i.e. its down-regulation as reflected by TorC1 reporter responses. We tested this assumption by performing head-to-head comparisons of the requirements for each condition to achieve a common outcome for a downstream proxy of TorC1 inactivation, nuclear Gln3 localization. We demonstrate that the five conditions for down-regulating TorC1 do not elicit physiologically equivalent outcomes. Four of the methods exhibit hierarchical Sit4 and PP2A phosphatase requirements to elicit nuclear Gln3-Myc13 localization. Rapamycin treatment required Sit4 and PP2A. Nitrogen limitation and short-term nitrogen starvation required only Sit4. G1 arrest-correlated, long-term nitrogen starvation and Msx treatment required neither PP2A nor Sit4. Starving cells of leucine or treating them with leucyl-tRNA synthetase inhibitors did not elicit nuclear Gln3-Myc13 localization. These data indicate that the five commonly used nitrogen-related conditions of down-regulating TorC1 are not physiologically equivalent and minimally involve partially differing regulatory mechanisms. Further, identical requirements for Msx treatment and long-term nitrogen starvation raise the possibility that their effects are achieved through a common regulatory pathway with glutamine, a glutamate or glutamine metabolite level as the sensed metabolic signal. PMID:23935103

  17. Immigration Rules, Regulations, and Requirements and Foreign Student Enrollments. Southeast Florida Education Consortium Workshop (Miami, Florida, February 18, 1981).

    ERIC Educational Resources Information Center

    Matthewson, Douglas E., Jr., Comp.

    Information is presented about a workshop on immigration documents, rules, regulations, and requirements associated with international students and nonimmigrant alien students. Twenty-six members of the Southeast Florida Educational Consortium participated, representing campus admissions and registrars offices, international student programs, and…

  18. 7 CFR 301.76-4 - Labeling requirements for regulated nursery stock produced within an area quarantined for citrus...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Citrus Greening and Asian Citrus Psyllid § 301.76-4 Labeling requirements for regulated nursery stock produced within an area quarantined for citrus greening... produced within an area quarantined for citrus greening. 301.76-4 Section 301.76-4 Agriculture...

  19. 75 FR 35338 - Implementation of Regulations Required Under Title XI of the Food, Conservation and Energy Act of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-22

    ...-AB07 Implementation of Regulations Required Under Title XI of the Food, Conservation and Energy Act of... participants regarding compliance. In enacting Title XI of the Food, Conservation and Energy Act of 2008 (Farm..., and its coverage was to encompass the complete chain of commerce and give the Secretary of...

  20. 77 FR 33638 - Amendment to the Bank Secrecy Act Regulations-Exemption From the Requirement To Report...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-07

    ...FinCEN is issuing this final rule to amend the regulations that allow depository institutions to exempt transactions of certain payroll customers \\1\\ from the requirement to report transactions in currency in excess of $10,000. The rule substitutes the term ``frequently'' for ``regularly'' in the provision of the exemption rules dealing with payroll customers. This modification of the......

  1. 77 FR 72970 - Revisions to Stormwater Regulations To Clarify That an NPDES Permit Is Not Required for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-07

    ...The EPA is revising its Phase I stormwater regulations to clarify that stormwater discharges from logging roads do not constitute stormwater discharges associated with industrial activity and that a National Pollutant Discharge Elimination System (NPDES) permit is not required for these stormwater...

  2. Caveolin-1–dependent occludin endocytosis is required for TNF-induced tight junction regulation in vivo

    PubMed Central

    Marchiando, Amanda M.; Shen, Le; Graham, W. Vallen; Weber, Christopher R.; Schwarz, Brad T.; Austin, Jotham R.; Raleigh, David R.; Guan, Yanfang; Watson, Alastair J.M.; Montrose, Marshall H.

    2010-01-01

    Epithelial paracellular barrier function, determined primarily by tight junction permeability, is frequently disrupted in disease. In the intestine, barrier loss can be mediated by tumor necrosis factor (α) (TNF) signaling and epithelial myosin light chain kinase (MLCK) activation. However, TNF induces only limited alteration of tight junction morphology, and the events that couple structural reorganization to barrier regulation have not been defined. We have used in vivo imaging and transgenic mice expressing fluorescent-tagged occludin and ZO-1 fusion proteins to link occludin endocytosis to TNF-induced tight junction regulation. This endocytosis requires caveolin-1 and is essential for structural and functional tight junction regulation. These data demonstrate that MLCK activation triggers caveolin-1–dependent endocytosis of occludin to effect structural and functional tight junction regulation. PMID:20351069

  3. 49 CFR 379.11 - Waiver of requirements of the regulations in this part.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... from any provision of the regulations in this part may be made by the Secretary upon his/her own initiative or upon submission of a written request by the company. Each request for waiver shall demonstrate... company....

  4. 49 CFR 379.11 - Waiver of requirements of the regulations in this part.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... from any provision of the regulations in this part may be made by the Secretary upon his/her own initiative or upon submission of a written request by the company. Each request for waiver shall demonstrate... company....

  5. 10 CFR 150.31 - Requirements for Agreement State regulation of byproduct material.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... with the requirements in appendix A of 10 CFR part 40 of this chapter to the maximum extent practicable... material, an Agreement State shall require: (1) Compliance with requirements in appendix A of 10 CFR part... in appendix A of 10 CFR part 40 of this chapter adopted and enforced by the Commission for the...

  6. 10 CFR 150.31 - Requirements for Agreement State regulation of byproduct material.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... with the requirements in appendix A of 10 CFR part 40 of this chapter to the maximum extent practicable... material, an Agreement State shall require: (1) Compliance with requirements in appendix A of 10 CFR part... in appendix A of 10 CFR part 40 of this chapter adopted and enforced by the Commission for the...

  7. 10 CFR 150.31 - Requirements for Agreement State regulation of byproduct material.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... with the requirements in appendix A of 10 CFR part 40 of this chapter to the maximum extent practicable... material, an Agreement State shall require: (1) Compliance with requirements in appendix A of 10 CFR part... in appendix A of 10 CFR part 40 of this chapter adopted and enforced by the Commission for the...

  8. 10 CFR 150.31 - Requirements for Agreement State regulation of byproduct material.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... with the requirements in appendix A of 10 CFR part 40 of this chapter to the maximum extent practicable... material, an Agreement State shall require: (1) Compliance with requirements in appendix A of 10 CFR part... in appendix A of 10 CFR part 40 of this chapter adopted and enforced by the Commission for the...

  9. 10 CFR 150.31 - Requirements for Agreement State regulation of byproduct material.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... with the requirements in appendix A of 10 CFR part 40 of this chapter to the maximum extent practicable... material, an Agreement State shall require: (1) Compliance with requirements in appendix A of 10 CFR part... in appendix A of 10 CFR part 40 of this chapter adopted and enforced by the Commission for the...

  10. Mycobacterium tuberculosis Phosphate Uptake System Component PstA2 Is Not Required for Gene Regulation or Virulence.

    PubMed

    Tischler, Anna D; Leistikow, Rachel L; Ramakrishnan, Pavithra; Voskuil, Martin I; McKinney, John D

    2016-01-01

    The Mycobacterium tuberculosis genome encodes two complete high-affinity Pst phosphate-specific transporters. We previously demonstrated that a membrane-spanning component of one Pst system, PstA1, was essential both for M. tuberculosis virulence and for regulation of gene expression in response to external phosphate availability. To determine if the alternative Pst system is similarly required for virulence or gene regulation, we constructed a deletion of pstA2. Transcriptome analysis revealed that PstA2 is not required for regulation of gene expression in phosphate-replete growth conditions. PstA2 was also dispensable for replication and virulence of M. tuberculosis in a mouse aerosol infection model. However, a ΔpstA1ΔpstA2 double mutant was attenuated in mice lacking the cytokine interferon-gamma, suggesting that M. tuberculosis requires high-affinity phosphate transport to survive phosphate limitation encountered in the host. Surprisingly, ΔpstA2 bacteria were more resistant to acid stress in vitro. This phenotype is intrinsic to the alternative Pst transporter since a ΔpstS1 mutant exhibited similar acid resistance. Our data indicate that the two M. tuberculosis Pst transporters have distinct physiological functions, with the PstA1 transporter being specifically involved in phosphate sensing and gene regulation while the PstA2 transporter influences survival in acidic conditions. PMID:27557082

  11. Mycobacterium tuberculosis Phosphate Uptake System Component PstA2 Is Not Required for Gene Regulation or Virulence

    PubMed Central

    Leistikow, Rachel L.; Ramakrishnan, Pavithra; Voskuil, Martin I.; McKinney, John D.

    2016-01-01

    The Mycobacterium tuberculosis genome encodes two complete high-affinity Pst phosphate-specific transporters. We previously demonstrated that a membrane-spanning component of one Pst system, PstA1, was essential both for M. tuberculosis virulence and for regulation of gene expression in response to external phosphate availability. To determine if the alternative Pst system is similarly required for virulence or gene regulation, we constructed a deletion of pstA2. Transcriptome analysis revealed that PstA2 is not required for regulation of gene expression in phosphate-replete growth conditions. PstA2 was also dispensable for replication and virulence of M. tuberculosis in a mouse aerosol infection model. However, a ΔpstA1ΔpstA2 double mutant was attenuated in mice lacking the cytokine interferon-gamma, suggesting that M. tuberculosis requires high-affinity phosphate transport to survive phosphate limitation encountered in the host. Surprisingly, ΔpstA2 bacteria were more resistant to acid stress in vitro. This phenotype is intrinsic to the alternative Pst transporter since a ΔpstS1 mutant exhibited similar acid resistance. Our data indicate that the two M. tuberculosis Pst transporters have distinct physiological functions, with the PstA1 transporter being specifically involved in phosphate sensing and gene regulation while the PstA2 transporter influences survival in acidic conditions. PMID:27557082

  12. Transcription factors of Lotus: regulation of isoflavonoid biosynthesis requires coordinated changes in transcription factor activity.

    PubMed

    Shelton, Dale; Stranne, Maria; Mikkelsen, Lisbeth; Pakseresht, Nima; Welham, Tracey; Hiraka, Hideki; Tabata, Satoshi; Sato, Shusei; Paquette, Suzanne; Wang, Trevor L; Martin, Cathie; Bailey, Paul

    2012-06-01

    Isoflavonoids are a class of phenylpropanoids made by legumes, and consumption of dietary isoflavonoids confers benefits to human health. Our aim is to understand the regulation of isoflavonoid biosynthesis. Many studies have shown the importance of transcription factors in regulating the transcription of one or more genes encoding enzymes in phenylpropanoid metabolism. In this study, we coupled bioinformatics and coexpression analysis to identify candidate genes encoding transcription factors involved in regulating isoflavonoid biosynthesis in Lotus (Lotus japonicus). Genes encoding proteins belonging to 39 of the main transcription factor families were examined by microarray analysis of RNA from leaf tissue that had been elicited with glutathione. Phylogenetic analyses of each transcription factor family were used to identify subgroups of proteins that were specific to L. japonicus or closely related to known regulators of the phenylpropanoid pathway in other species. R2R3MYB subgroup 2 genes showed increased expression after treatment with glutathione. One member of this subgroup, LjMYB14, was constitutively overexpressed in L. japonicus and induced the expression of at least 12 genes that encoded enzymes in the general phenylpropanoid and isoflavonoid pathways. A distinct set of six R2R3MYB subgroup 2-like genes was identified. We suggest that these subgroup 2 sister group proteins and those belonging to the main subgroup 2 have roles in inducing isoflavonoid biosynthesis. The induction of isoflavonoid production in L. japonicus also involves the coordinated down-regulation of competing biosynthetic pathways by changing the expression of other transcription factors. PMID:22529285

  13. Profiles of Motivated Self-Regulation in College Computer Science Courses: Differences in Major versus Required Non-Major Courses

    NASA Astrophysics Data System (ADS)

    Shell, Duane F.; Soh, Leen-Kiat

    2013-12-01

    The goal of the present study was to utilize a profiling approach to understand differences in motivation and strategic self-regulation among post-secondary STEM students in major versus required non-major computer science courses. Participants were 233 students from required introductory computer science courses (194 men; 35 women; 4 unknown) at a large Midwestern state university. Cluster analysis identified five profiles: (1) a strategic profile of a highly motivated by-any-means good strategy user; (2) a knowledge-building profile of an intrinsically motivated autonomous, mastery-oriented student; (3) a surface learning profile of a utility motivated minimally engaged student; (4) an apathetic profile of an amotivational disengaged student; and (5) a learned helpless profile of a motivated but unable to effectively self-regulate student. Among CS majors and students in courses in their major field, the strategic and knowledge-building profiles were the most prevalent. Among non-CS majors and students in required non-major courses, the learned helpless, surface learning, and apathetic profiles were the most prevalent. Students in the strategic and knowledge-building profiles had significantly higher retention of computational thinking knowledge than students in other profiles. Students in the apathetic and surface learning profiles saw little instrumentality of the course for their future academic and career objectives. Findings show that students in STEM fields taking required computer science courses exhibit the same constellation of motivated strategic self-regulation profiles found in other post-secondary and K-12 settings.

  14. Fusarium verticillioides SGE1 is required for full virulence and regulates expression of protein effector and secondary metabolite biosynthetic genes.

    PubMed

    Brown, Daren W; Busman, Mark; Proctor, Robert H

    2014-08-01

    The transition from one lifestyle to another in some fungi is initiated by a single orthologous gene, SGE1, that regulates markedly different genes in different fungi. Despite these differences, many of the regulated genes encode effector proteins or proteins involved in the synthesis of secondary metabolites (SM), both of which can contribute to pathogenicity. Fusarium verticillioides is both an endophyte and a pathogen of maize and can grow as a saprophyte on dead plant material. During growth on live maize plants, the fungus can synthesize a number of toxic SM, including fumonisins, fusarins, and fusaric acid, that can contaminate kernels and kernel-based food and feed. In this study, the role of F. verticillioides SGE1 in pathogenicity and secondary metabolism was examined by gene deletion analysis and transcriptomics. SGE1 is not required for vegetative growth or conidiation but is required for wild-type pathogenicity and affects synthesis of multiple SM, including fumonisins and fusarins. Induced expression of SGE1 enhanced or reduced expression of hundreds of genes, including numerous putative effector genes that could contribute to growth in planta; genes encoding cell surface proteins; gene clusters required for synthesis of fusarins, bikaverin, and an unknown metabolite; as well as the gene encoding the fumonisin cluster transcriptional activator. Together, our results indicate that SGE1 has a role in global regulation of transcription in F. verticillioides that impacts but is not absolutely required for secondary metabolism and pathogenicity on maize. PMID:24742071

  15. 78 FR 63461 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Foreign...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-24

    ... Payments Program Certificate, as prescribed in 225.1101(1), requires an offeror to identify, in its... in 225.1101(4), requires the contractor to provide information on shipping documents and customs... of origin. DFARS 252.225-7020, Trade Agreements Certificate, as prescribed in 225.1101(5),...

  16. 77 FR 12927 - Federal Acquisition Regulation: Requirements for Acquisitions Pursuant to Multiple-Award Contracts

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-02

    .... Background DoD, GSA, and NASA published an interim rule in the Federal Register at 76 FR 14548 on March 16... Register at 76 FR 14548 on March 16, 2011, is adopted as final with the following changes: PART 8--REQUIRED...; (5) Competition requirements for establishing BPAs and allowing flexibility in establishing...

  17. 76 FR 17138 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-28

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Clinical Trial Requirements... public workshop on FDA's clinical trial requirements is designed to aid the clinical research... interaction with FDA representatives. The program will focus on the relationships among FDA and clinical...

  18. 76 FR 78933 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-20

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Clinical Trial Requirements... workshop. The public workshop on FDA's clinical trial requirements is designed to aid the clinical research... interaction with FDA representatives. The program will focus on the relationships among FDA and clinical...

  19. 75 FR 51824 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-23

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Clinical Trial Requirements... workshop. The public workshop on FDA's clinical trial requirements is designed to aid the clinical research... interaction with FDA representatives. The program will focus on the relationships among FDA and clinical...

  20. 76 FR 51040 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-17

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Clinical Trial Requirements... workshop. The public workshop on FDA's clinical trial requirements is designed to aid the clinical research... interaction with FDA representatives. The program will focus on the relationships among FDA and clinical...

  1. 77 FR 8886 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-15

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Clinical Trial Requirements... public workshop on FDA's clinical trial requirements is designed to aid the clinical research... interaction with FDA representatives. The program will focus on the relationships among FDA and clinical...

  2. 33 CFR 165.921 - Regulated Navigation Area; Reporting Requirements for Barges Loaded with Certain Dangerous...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... in this section— Barge means a non-self propelled vessel engaged in commerce, as set out in 33 CFR... explosives as defined in 49 CFR 173.50. (2) Division 1.5D blasting agents for which a permit is required under 49 CFR 176.415 or, for which a permit is required as a condition of a Research and...

  3. 33 CFR 165.921 - Regulated Navigation Area; Reporting Requirements for Barges Loaded with Certain Dangerous...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... in this section— Barge means a non-self propelled vessel engaged in commerce, as set out in 33 CFR... explosives as defined in 49 CFR 173.50. (2) Division 1.5D blasting agents for which a permit is required under 49 CFR 176.415 or, for which a permit is required as a condition of a Research and...

  4. 33 CFR 165.921 - Regulated Navigation Area; Reporting Requirements for Barges Loaded with Certain Dangerous...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... in this section— Barge means a non-self propelled vessel engaged in commerce, as set out in 33 CFR... explosives as defined in 49 CFR 173.50. (2) Division 1.5D blasting agents for which a permit is required under 49 CFR 176.415 or, for which a permit is required as a condition of a Research and...

  5. 77 FR 51686 - Specialty Crops; Import Regulations; New Pistachio Import Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-27

    ... in the marketing order for domestic pistachios as established at 69 FR 17844 (April 5, 2004) and amended at 74 FR 56532 (November 2, 2009). Under the new regulation, ``pistachio'' means the nut of the... testing procedures that align with the Codex Alimentarius Commission's (Codex) sampling plan (75 FR...

  6. 76 FR 71465 - Defense Federal Acquisition Regulations Supplement; Notification Requirements for Awards of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-18

    ... Contracts (DFARS Case 2009-D036) AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD... Logistics) Defense Procurement and Acquisition Policy (DPAP) Contract Policy and International Contracting... the senior procurement executive. (ii) The head of the agency must notify the congressional...

  7. Regulation of Hepatic Triacylglycerol Metabolism by CGI-58 Does Not Require ATGL Co-activation.

    PubMed

    Lord, Caleb C; Ferguson, Daniel; Thomas, Gwynneth; Brown, Amanda L; Schugar, Rebecca C; Burrows, Amy; Gromovsky, Anthony D; Betters, Jenna; Neumann, Chase; Sacks, Jessica; Marshall, Stephanie; Watts, Russell; Schweiger, Martina; Lee, Richard G; Crooke, Rosanne M; Graham, Mark J; Lathia, Justin D; Sakaguchi, Takuya F; Lehner, Richard; Haemmerle, Guenter; Zechner, Rudolf; Brown, J Mark

    2016-07-26

    Adipose triglyceride lipase (ATGL) and comparative gene identification 58 (CGI-58) are critical regulators of triacylglycerol (TAG) turnover. CGI-58 is thought to regulate TAG mobilization by stimulating the enzymatic activity of ATGL. However, it is not known whether this coactivation function of CGI-58 occurs in vivo. Moreover, the phenotype of human CGI-58 mutations suggests ATGL-independent functions. Through direct comparison of mice with single or double deficiency of CGI-58 and ATGL, we show here that CGI-58 knockdown causes hepatic steatosis in both the presence and absence of ATGL. CGI-58 also regulates hepatic diacylglycerol (DAG) and inflammation in an ATGL-independent manner. Interestingly, ATGL deficiency, but not CGI-58 deficiency, results in suppression of the hepatic and adipose de novo lipogenic program. Collectively, these findings show that CGI-58 regulates hepatic neutral lipid storage and inflammation in the genetic absence of ATGL, demonstrating that mechanisms driving TAG lipolysis in hepatocytes differ significantly from those in adipocytes. PMID:27396333

  8. 75 FR 81337 - Interim Final Regulation Deferring the Reporting Date for Certain Data Elements Required Under...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-27

    ... of Federal Regulations EPA U.S. Environmental Protection Agency FR Federal Register GHG greenhouse... FR 56371, October 30, 2009). G. Executive Order 13045: Protection of Children From Environmental... From the Federal Register Online via the Government Publishing Office ] Part II...

  9. A Comparison of the Mandatory Continuing Education (MCE) Requirements of the Regulated Health Occupations in Minnesota.

    ERIC Educational Resources Information Center

    Green-Eide, Beth

    A study reviewed and compared initial and renewal practices for licensure/registration of 13 health care occupations regulated in the state of Minnesota. It examined mandatory continuing education (MCE) documentation and the practices of licensing boards in their enforcement of the MCE legislation. The Minnesota Statutes and Rules for the…

  10. 78 FR 4032 - Prompt Corrective Action, Requirements for Insurance, and Promulgation of NCUA Rules and Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-18

    ... amendment to 12 CFR 791.8. \\1\\ IRPS 03-2, 68 FR 31949 (May 29, 2003). What changes were proposed? On... rule governing the promulgation of regulations.\\9\\ \\6\\ 46 FR 29248 (June 1, 1981). \\7\\ 52 FR 35231 (Sept. 8, 1987). \\8\\ 68 FR at 31949. \\9\\ 12 CFR 791.8(a). When the Board updated its RFA threshold...

  11. 78 FR 20624 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement (DFARS...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-05

    ... Regulation Supplement (DFARS); Radio Frequency Identification Advance Shipment Notices AGENCY: Defense... Supplement (DFARS), Part 211 and related clause at 252.211; Radio Frequency Identification Advance Shipment.... Annual Burden Hours: 31,556. Frequency: On occasion. Summary of Information Collection The clause...

  12. 75 FR 68330 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-05

    ... Regulation Supplement; Occupational Safety and Drug-Free Work Force (OMB Control Number 0704-0272) AGENCY... 223, Occupational Safety and Drug-Free Work Force, and related clauses in DFARS 252.223; OMB Control...; Identify the place of performance of all ammunition and explosives work; and Ensure contractor...

  13. 75 FR 69423 - Information Collection Requirements; Defense Federal Acquisition Regulation Supplement; Small...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-12

    ... Control Number 0704-0386. Needs and Uses: DoD uses this information in assessing contractor compliance... Regulations System, Department of Defense (DoD). ACTION: Notice and request for comments regarding a proposed...)(A) of the Paperwork Reduction Act of 1995 (44 U.S.C. chapter 35), DoD announces the...

  14. 77 FR 74177 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Production...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-13

    ... Acquisition Regulations System, Department of Defense (DoD). ACTION: Notice; request for comments regarding a... 3506(c)(2)(A) of the Paperwork Reduction Act of 1995 (44 U.S.C. Chapter 35), DoD announces the proposed.... DoD invites comments on: (a) Whether the proposed collection of information is necessary for...

  15. 75 FR 3617 - Outer Continental Shelf Air Regulations Update To Include New Jersey State Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-22

    ... degrees longitude. \\1\\ The reader may refer to the Proposed Rulemaking, December 5, 1991 (56 FR 63774), and the preamble to the final rule promulgated September 4, 1992 (57 FR 40792) for further background and information on the OCS regulations. On October 2, 2009 (74 FR 50939), EPA proposed to...

  16. 75 FR 6185 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Rights in...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-08

    ... Regulation Supplement; Rights in Technical Data and Computer Software (OMB Control Number 0704-0369) AGENCY... Subpart 227.72, Rights in Computer Software and Computer Software Documentation, and related provisions... technical data and computer software. DoD needs this information to implement 10 U.S.C. 2320, Rights...

  17. 27 CFR 70.411 - Imposition of taxes, qualification requirements, and regulations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...: (1) Establishment and operation of distilled spirits plants. Part 19 of title 27 CFR contains the... vaporizing process. (2) Miscellaneous liquor transactions. Part 29 of 27 CFR contains miscellaneous... 27 CFR contains the regulations that. prescribe the gauging instruments, and methods or techniques...

  18. 78 FR 69267 - Defense Federal Acquisition Regulation Supplement: Requirements Relating to Supply Chain Risk...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-18

    ...DoD is issuing an interim rule amending the Defense Federal Acquisition Regulation Supplement (DFARS) to implement a section of the National Defense Authorization Act (NDAA) for Fiscal Year (FY) 2011, as amended by the NDAA for FY 2013. This interim rule allows DoD to consider the impact of supply chain risk in specified types of procurements related to national security...

  19. NOVA2-mediated RNA regulation is required for axonal pathfinding during development

    PubMed Central

    Saito, Yuhki; Miranda-Rottmann, Soledad; Ruggiu, Matteo; Park, Christopher Y; Fak, John J; Zhong, Ru; Duncan, Jeremy S; Fabella, Brian A; Junge, Harald J; Chen, Zhe; Araya, Roberto; Fritzsch, Bernd; Hudspeth, A J; Darnell, Robert B

    2016-01-01

    The neuron specific RNA-binding proteins NOVA1 and NOVA2 are highly homologous alternative splicing regulators. NOVA proteins regulate at least 700 alternative splicing events in vivo, yet relatively little is known about the biologic consequences of NOVA action and in particular about functional differences between NOVA1 and NOVA2. Transcriptome-wide searches for isoform-specific functions, using NOVA1 and NOVA2 specific HITS-CLIP and RNA-seq data from mouse cortex lacking either NOVA isoform, reveals that NOVA2 uniquely regulates alternative splicing events of a series of axon guidance related genes during cortical development. Corresponding axonal pathfinding defects were specific to NOVA2 deficiency: Nova2-/- but not Nova1-/- mice had agenesis of the corpus callosum, and axonal outgrowth defects specific to ventral motoneuron axons and efferent innervation of the cochlea. Thus we have discovered that NOVA2 uniquely regulates alternative splicing of a coordinate set of transcripts encoding key components in cortical, brainstem and spinal axon guidance/outgrowth pathways during neural differentiation, with severe functional consequences in vivo. DOI: http://dx.doi.org/10.7554/eLife.14371.001 PMID:27223325

  20. Follicle-stimulating hormone/cAMP regulation of aromatase gene expression requires β-catenin

    PubMed Central

    Parakh, Tehnaz N.; Hernandez, Jennifer A.; Grammer, Jean C.; Weck, Jennifer; Hunzicker-Dunn, Mary; Zeleznik, Anthony J.; Nilson, John H.

    2006-01-01

    Estrogens profoundly influence the physiology and pathology of reproductive and other tissues. Consequently, emphasis has been placed on delineating the mechanisms underlying regulation of estrogen levels. Circulating levels of estradiol in women are controlled by follicle-stimulating hormone (FSH), which regulates transcription of the aromatase gene (CYP19A1) in ovarian granulosa cells. Previous studies have focused on two downstream effectors of the FSH signal, cAMP and the orphan nuclear receptor steroidogenic factor-1 (NR5A1). In this report, we present evidence for β-catenin (CTNNB1) as an essential transcriptional regulator of CYP19A1. FSH induction of select steroidogenic enzyme mRNAs, including Cyp19a1, is enhanced by β-catenin. Additionally, β-catenin is present in transcription complexes assembled on the endogenous gonad-specific CYP19A1 promoter, as evidenced by chromatin immunoprecipitation assays. Transient expression and RNAi studies demonstrate that FSH- and cAMP-dependent regulation of this promoter is sensitive to alterations in the level of β-catenin. The stimulatory effect of β-catenin is mediated through functional interactions with steroidogenic factor-1 that involve four acidic residues within its ligand-binding domain, mutation of which attenuates FSH/cAMP-induced Cyp19a1 mRNA accumulation. Together, these data demonstrate that β-catenin is essential for FSH/cAMP-regulated gene expression in the ovary, identifying a central and previously unappreciated role for β-catenin in estrogen biosynthesis, and a potential broader role in other aspects of follicular maturation. PMID:16895991

  1. ECM-Regulator timp Is Required for Stem Cell Niche Organization and Cyst Production in the Drosophila Ovary

    PubMed Central

    Pearson, John R.; Zurita, Federico; Tomás-Gallardo, Laura; Díaz-Torres, Alfonsa; Díaz de la Loza, María del Carmen; Franze, Kristian; Martín-Bermudo, María D.; González-Reyes, Acaimo

    2016-01-01

    The extracellular matrix (ECM) is a pivotal component adult tissues and of many tissue-specific stem cell niches. It provides structural support and regulates niche signaling during tissue maintenance and regeneration. In many tissues, ECM remodeling depends on the regulation of MMP (matrix metalloproteinase) activity by inhibitory TIMP (tissue inhibitors of metalloproteinases) proteins. Here, we report that the only Drosophila timp gene is required for maintaining the normal organization and function of the germline stem cell niche in adult females. timp mutant ovaries show reduced levels of both Drosophila Collagen IV α chains. In addition, tissue stiffness and the cellular organization of the ovarian niche are affected in timp mutants. Finally, loss of timp impairs the ability of the germline stem cell niche to generate new cysts. Our results demonstrating a crucial role for timp in tissue organization and gamete production thus provide a link between the regulation of ECM metabolism and tissue homeostasis. PMID:26808525

  2. Cis-acting elements are required for selenium regulation of glutathione peroxidase-1 mRNA levels.

    PubMed Central

    Weiss, S L; Sunde, R A

    1998-01-01

    Classical glutathione peroxidase (GPX1) mRNA levels can decrease to less than 10% in selenium (Se)-deficient rat liver. The cis-acting nucleic acid sequence requirements for Se regulation of GPX1 mRNA levels were studied by transfecting Chinese hamster ovary (CHO) cells with GPX1 DNA constructs in which specific regions of the GPX1 gene were mutated, deleted, or replaced by comparable regions from unregulated genes such as phospholipid hydroperoxide glutathione peroxidase (GPX4). For each construct, stable transfectants were pooled two weeks after transfection, divided into Se-deficient (2 nM Se) or Se-adequate (200 nM Se) medium, and grown for an additional four days. On day of harvest, Se-deficient GPX1 and GPX4 activities averaged 13 +/- 2% and 15 +/- 2% of Se adequate levels, confirming that cellular Se status was dramatically altered by Se supplementation. RNA was isolated from replicate plates of cells and transfected mRNA levels were specifically determined by RNase protection assay. Analysis of chimeric GPX1/GPX4 constructs showed that the GPX4 3'-UTR can completely replace the GPX1 3'-UTR in Se regulation of GPX1 mRNA. We did not find any GPX1 coding regions that could be replaced by the corresponding GPX4 coding regions without diminishing or eliminating Se regulation of the transfected GPX1 mRNA. Further analysis of the GPX1 coding region demonstrated that the GPX1 Sec codon (UGA) and the GPX1 intron sequences are required for full Se regulation of transfected GPX1 mRNA levels. Mutations that moved the GPX1 Sec codon to three different positions within the GPX1 coding region suggest that the mechanism for Se regulation of GPX1 mRNA requires a Sec codon within exon 1. Lastly, we found that addition of the GPX1 3'-UTR to beta-globin mRNA can convey significant Se regulation to beta-globin mRNA levels when a UGA codon is placed within exon 1. We conclude that Se regulation of GPX1 mRNA requires a functional selenocysteine insertion sequence (SECIS) in the 3

  3. 76 FR 24443 - Federal Acquisition Regulation; Service Contracts Reporting Requirements; Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-02

    ... (202) 501-0044. Please cite FAR Case 2010-010. Correction In the proposed rule FR Doc. 2011-9515... simplified acquisition threshold (SAT). Contractors will be required to report on new fixed-price...

  4. Drosophila Fatty Acid Transport Protein Regulates Rhodopsin-1 Metabolism and Is Required for Photoreceptor Neuron Survival

    PubMed Central

    Dourlen, Pierre; Bertin, Benjamin; Chatelain, Gilles; Robin, Marion; Napoletano, Francesco; Roux, Michel J.; Mollereau, Bertrand

    2012-01-01

    Tight regulation of the visual response is essential for photoreceptor function and survival. Visual response dysregulation often leads to photoreceptor cell degeneration, but the causes of such cell death are not well understood. In this study, we investigated a fatty acid transport protein (fatp) null mutation that caused adult-onset and progressive photoreceptor cell death. Consistent with fatp having a role in the retina, we showed that fatp is expressed in adult photoreceptors and accessory cells and that its re-expression in photoreceptors rescued photoreceptor viability in fatp mutants. The visual response in young fatp-mutant flies was abnormal with elevated electroretinogram amplitudes associated with high levels of Rhodopsin-1 (Rh1). Reducing Rh1 levels in rh1 mutants or depriving flies of vitamin A rescued photoreceptor cell death in fatp mutant flies. Our results indicate that fatp promotes photoreceptor survival by regulating Rh1 abundance. PMID:22844251

  5. Down-regulation of epithelial cadherin is required to initiate metastatic outgrowth of breast cancer

    PubMed Central

    Wendt, Michael K.; Taylor, Molly A.; Schiemann, Barbara J.; Schiemann, William P.

    2011-01-01

    Reduced epithelial cadherin (E-cad) is a hallmark of invasive carcinomas that have acquired epithelial-mesenchymal transition (EMT) phenotypes. Here we show that down-regulated E-cad expression induced by transforming growth factor-β (TGF-β) and EMT preceded breast cancer outgrowth in three-dimensional (3D) organotypic assays and in the lungs of mice. Pharmacological inhibitors against focal adhesion kinase prevented metastatic outgrowth of newly seeded organoids, but not that of their fully established counterparts. Interrogating the D2-HAN (hyperplastic alveolar nodule) model of breast cancer dormancy and metastasis showed that dormant D2.OR cells produced branched organoid morphologies in 3D-cultures, and expressed robust quantities of E-cad that was uncoupled from regulation by TGF-β. In contrast, metastatic D2.A1 organoids were spherical and wholly lacked E-cad expression. Interestingly, D2.A1 cells engineered to re-express E-cad formed branched organoids, down-regulated β1 integrin expression, and failed to undergo metastatic outgrowth. The tumor-suppressing function of E-cad was inactivated by increased microenvironmental rigidity, and was not recapitulated by expression of an E-cad mutant lacking its extracellular domain. Twist expression, but not that of Snail, reinitiated metastatic outgrowth in dormant D2.OR cells. Our findings show that EMT and its down-regulated expression of E-cad circumvent breast cancer dormancy in part by facilitating β1 integrin expression necessary for metastatic outgrowth. PMID:21613543

  6. UVRAG is required for organ rotation by regulating Notch endocytosis in Drosophila

    PubMed Central

    Lee, Gina; Liang, Chengyu; Park, Gihyun; Jang, Cholsoon; Jung, Jae U.; Chung, Jongkyeong

    2015-01-01

    Heterotaxy characterized by abnormal left–right body asymmetry causes diverse congenital anomalies. Organ rotation is a crucial developmental process to establish the left–right patterning during animal development. However, the molecular basis of how organ rotation is regulated is poorly understood. Here we report that Drosophila UV-resistance associated gene (UVRAG), a tumor suppressor that regulates autophagy and endocytosis, plays unexpected roles in controlling organ rotation. Loss-of-function mutants of UVRAG show seriously impaired organ rotation phenotypes, which are associated with defects in endocytic trafficking rather than autophagy. Blunted endocytic degradation by UVRAG deficiency causes endosomal accumulation of Notch, resulting in abnormally enhanced Notch activity. Knockdown of Notch itself or expression of a dominant negative form of Notch transcriptional co-activator Mastermind is sufficient to rescue the rotation defect in UVRAG mutants. Consistently, UVRAG-mutated heterotaxy patient cells also display highly increased Notch protein levels. These results suggest evolutionarily conserved roles of UVRAG in organ rotation by regulating Notch endocytic degradation. PMID:21729695

  7. Up-regulation of glycolytic metabolism is required for HIF1α-driven bone formation.

    PubMed

    Regan, Jenna N; Lim, Joohyun; Shi, Yu; Joeng, Kyu Sang; Arbeit, Jeffrey M; Shohet, Ralph V; Long, Fanxin

    2014-06-10

    The bone marrow environment is among the most hypoxic in the body, but how hypoxia affects bone formation is not known. Because low oxygen tension stabilizes hypoxia-inducible factor alpha (HIFα) proteins, we have investigated the effect of expressing a stabilized form of HIF1α in osteoblast precursors. Brief stabilization of HIF1α in SP7-positive cells in postnatal mice dramatically stimulated cancellous bone formation via marked expansion of the osteoblast population. Remarkably, concomitant deletion of vascular endothelial growth factor A (VEGFA) in the mouse did not diminish bone accrual caused by HIF1α stabilization. Thus, HIF1α-driven bone formation is independent of VEGFA up-regulation and increased angiogenesis. On the other hand, HIF1α stabilization stimulated glycolysis in bone through up-regulation of key glycolytic enzymes including pyruvate dehydrogenase kinase 1 (PDK1). Pharmacological inhibition of PDK1 completely reversed HIF1α-driven bone formation in vivo. Thus, HIF1α stimulates osteoblast formation through direct activation of glycolysis, and alterations in cellular metabolism may be a broadly applicable mechanism for regulating cell differentiation. PMID:24912186

  8. Requirements for Cell Rounding and Surface Protein Down-Regulation by Ebola Virus Glycoprotein

    PubMed Central

    Francica, Joseph R.; Matukonis, Meghan K.; Bates, Paul

    2009-01-01

    Ebola virus causes an acute hemorrhagic fever that is associated with high morbidity and mortality. The viral glycoprotein is thought to contribute to pathogenesis, though precise mechanisms are unknown. Cellular pathogenesis can be modeled in vitro by expression of the Ebola viral glycoprotein (GP) in cells, which causes dramatic morphological changes, including cell rounding and surface protein down-regulation. These effects are known to be dependent on the presence of a highly glycosylated region of the glycoprotein, the mucin domain. Here we show that the mucin domain from the highly pathogenic Zaire subtype of Ebola virus is sufficient to cause characteristic cytopathology when expressed in the context of a foreign glycoprotein. Similarly to full length Ebola GP, expression of the mucin domain causes rounding, detachment from the extracellular matrix, and the down-regulation of cell surface levels of β1 integrin and major histocompatibility complex class 1. These effects were not seen when the mucin domain was expressed in the context of a glycophosphatidylinositol-anchored isoform of the foreign glycoprotein. In contrast to earlier analysis of full length Ebola glycoproteins, chimeras carrying the mucin domains from the Zaire and Reston strains appear to cause similar levels of down-modulation and cell detachment. Cytopathology associated with Ebola glycoprotein expression does not occur when GP expression is restricted to the endoplasmic reticulum. In contrast to a previously published report, our results demonstrate that GP-induced surface protein down-regulation is not mediated through a dynamin-dependent pathway. Overall, these results support a model in which the mucin domain of Ebola GP acts at the cell surface to induce protein down modulation and cytopathic effects. PMID:19013626

  9. Regulation of Motility Behavior in Myxococcus xanthus May Require an Extracytoplasmic-Function Sigma Factor

    PubMed Central

    Ward, Mandy J.; Lew, Helen; Treuner-Lange, Anke; Zusman, David R.

    1998-01-01

    Using interaction trap technology, we identified a putative extracytoplasmic-function (ECF) sigma factor (RpoE1) in Myxococcus xanthus, a bacterium which has a complex life cycle that includes fruiting body formation. The first domain of the response regulator protein FrzZ, a component of the Frz signal transduction system, was used as bait. Although the RpoE1 protein displayed no interactions with control proteins presented as bait, a weak interaction with a second M. xanthus response regulator (AsgA) was observed. While the specificity of the FrzZ-RpoE1 interaction therefore remains speculative, cloning and sequencing of the region surrounding rpoE1 localized it to a position downstream of the frzZ gene. A potential promoter site for binding of an ECF sigma factor was identified upstream of rpoE1, suggesting the gene may be autoregulated. However, primer extension studies suggested that transcription of rpoE1 occurs under both vegetative and developmental conditions from a ς70-like promoter. Dot blot analysis of RNA preparations confirmed the low-level, constitutive expression of rpoE1 during both stages of the life cycle. Analysis of an insertion mutant also indicated a role for RpoE1 under both vegetative and developmental conditions, since swarming was reduced on nutrient-rich agar and developmental aggregation was effected under starvation conditions, especially at high cell densities. An insertion mutation introduced into the gene directly downstream of rpoE1 (orf5) did not result in either swarming or developmental aggregation defects, even though the gene is transcribed as part of the same operon. Therefore, we propose that this new ECF sigma factor could play a role in the transcriptional regulation of genes involved in motility behavior during both stages of the complex M. xanthus life cycle. PMID:9791117

  10. Requirements for Ion and Solute Transport, and pH Regulation During Enamel Maturation

    PubMed Central

    LACRUZ, RODRIGO S.; SMITH, CHARLES E.; MOFFATT, PIERRE; CHANG, EUGENE H.; BROMAGE, TIMOTHY G.; BRINGAS, PABLO; NANCI, ANTONIO; BANIWAL, SANJEEV K.; ZABNER, JOSEPH; WELSH, MICHAEL J.; KURTZ, IRA; PAINE, MICHAEL L.

    2012-01-01

    Transcellular bicarbonate transport is suspected to be an important pathway used by ameloblasts to regulate extracellular pH and support crystal growth during enamel maturation. Proteins that play a role in amelogenesis include members of the ABC transporters (SLC gene family and CFTR). A number of carbonic anhydrases (CAs) have also been identified. The defined functions of these genes are likely interlinked during enamel mineralization. The purpose of this study is to quantify relative mRNA levels of individual SLC, Cftr, and CAs in enamel cells obtained from secretory and maturation stages on rat incisors. We also present novel data on the enamel phenotypes for two animal models, amutant porcine(CFTR-ΔF508) and the NBCe1-null mouse.Our data show that two SLCs(AE2 and NBCe1),Cftr,and Car2, Car3,Car6,and Car12 are all significantly up-regulated at the onset of the maturation stage of amelogenesis when compared to the secretory stage. The remaining SLCs and CA gene transcripts showed negligible expression or no significant change in expression from secretory to maturation stages. The enamel of Cftr-ΔF508 adult pigs was hypomineralized and showed abnormal crystal growth. NBCe1-null mice enamel was structurally defective and had a marked decrease in mineral content relative to wild-type. These data demonstrate the importance of many non-matrix proteins to amelogenesis and that the expression levels of multiple genes regulating extracellular pH are modulated during enamel maturation in response to an increased need for pH buffering during hydroxyapatite crystal growth. PMID:21732355

  11. Requirements for ion and solute transport, and pH regulation during enamel maturation.

    PubMed

    Lacruz, Rodrigo S; Smith, Charles E; Moffatt, Pierre; Chang, Eugene H; Bromage, Timothy G; Bringas, Pablo; Nanci, Antonio; Baniwal, Sanjeev K; Zabner, Joseph; Welsh, Michael J; Kurtz, Ira; Paine, Michael L

    2012-04-01

    Transcellular bicarbonate transport is suspected to be an important pathway used by ameloblasts to regulate extracellular pH and support crystal growth during enamel maturation. Proteins that play a role in amelogenesis include members of the ABC transporters (SLC gene family and CFTR). A number of carbonic anhydrases (CAs) have also been identified. The defined functions of these genes are likely interlinked during enamel mineralization. The purpose of this study is to quantify relative mRNA levels of individual SLC, Cftr, and CAs in enamel cells obtained from secretory and maturation stages on rat incisors. We also present novel data on the enamel phenotypes for two animal models, a mutant porcine (CFTR-ΔF508) and the NBCe1-null mouse. Our data show that two SLCs (AE2 and NBCe1), Cftr, and Car2, Car3, Car6, and Car12 are all significantly up-regulated at the onset of the maturation stage of amelogenesis when compared to the secretory stage. The remaining SLCs and CA gene transcripts showed negligible expression or no significant change in expression from secretory to maturation stages. The enamel of CFTR-ΔF508 adult pigs was hypomineralized and showed abnormal crystal growth. NBCe1-null mice enamel was structurally defective and had a marked decrease in mineral content relative to wild-type. These data demonstrate the importance of many non-matrix proteins to amelogenesis and that the expression levels of multiple genes regulating extracellular pH are modulated during enamel maturation in response to an increased need for pH buffering during hydroxyapatite crystal growth. PMID:21732355

  12. Leptin is required for hypothalamic regulation of miRNAs targeting POMC 3′UTR

    PubMed Central

    Derghal, Adel; Djelloul, Mehdi; Airault, Coraline; Pierre, Clément; Dallaporta, Michel; Troadec, Jean-Denis; Tillement, Vanessa; Tardivel, Catherine; Bariohay, Bruno; Trouslard, Jérôme; Mounien, Lourdes

    2015-01-01

    The central nervous system (CNS) monitors modifications in metabolic parameters or hormone levels and elicits adaptive responses such as food intake regulation. Particularly, within the hypothalamus, leptin modulates the activity of pro-opiomelanocortin (POMC) neurons which are critical regulators of energy balance. Consistent with a pivotal role of the melanocortin system in the control of energy homeostasis, disruption of the POMC gene causes hyperphagia and obesity. MicroRNAs (miRNAs) are short noncoding RNA molecules that post-transcriptionally repress the expression of genes by binding to 3′-untranslated regions (3′UTR) of the target mRNAs. However, little is known regarding the role of miRNAs that target POMC 3′UTR in the central control energy homeostasis. Particularly, their interaction with the leptin signaling pathway remain unclear. First, we used common prediction programs to search for potential miRNAs target sites on 3′UTR of POMC mRNA. This screening identified a set of conserved miRNAs seed sequences for mir-383, mir-384-3p, and mir-488. We observed that mir-383, mir-384-3p, and mir-488 are up-regulated in the hypothalamus of leptin deficient ob/ob mice. In accordance with these observations, we also showed that mir-383, mir-384-3p, and mir-488 were increased in db/db mice that exhibit a non-functional leptin receptor. The intraperitoneal injection of leptin down-regulated the expression of these miRNAs of interest in the hypothalamus of ob/ob mice showing the involvement of leptin in the expression of mir-383, mir-384-3p, and mir-488. Finally, the evaluation of responsivity to intracerebroventricular administration of leptin exhibited that a chronic treatment with leptin decreased mir-488 expression in hypothalamus of C57BL/6 mice. In summary, these results suggest that leptin modulates the expression of miRNAs that target POMC mRNA in hypothalamus. PMID:25999818

  13. A Mechanism Regulating G Protein-coupled Receptor Signaling That Requires Cycles of Protein Palmitoylation and Depalmitoylation* ♦

    PubMed Central

    Jia, Lixia; Chisari, Mariangela; Maktabi, Mohammad H.; Sobieski, Courtney; Zhou, Hao; Konopko, Aaron M.; Martin, Brent R.; Mennerick, Steven J.; Blumer, Kendall J.

    2014-01-01

    Reversible attachment and removal of palmitate or other long-chain fatty acids on proteins has been hypothesized, like phosphorylation, to control diverse biological processes. Indeed, palmitate turnover regulates Ras trafficking and signaling. Beyond this example, however, the functions of palmitate turnover on specific proteins remain poorly understood. Here, we show that a mechanism regulating G protein-coupled receptor signaling in neuronal cells requires palmitate turnover. We used hexadecyl fluorophosphonate or palmostatin B to inhibit enzymes in the serine hydrolase family that depalmitoylate proteins, and we studied R7 regulator of G protein signaling (RGS)-binding protein (R7BP), a palmitoylated allosteric modulator of R7 RGS proteins that accelerate deactivation of Gi/o class G proteins. Depalmitoylation inhibition caused R7BP to redistribute from the plasma membrane to endomembrane compartments, dissociated R7BP-bound R7 RGS complexes from Gi/o-gated G protein-regulated inwardly rectifying K+ (GIRK) channels and delayed GIRK channel closure. In contrast, targeting R7BP to the plasma membrane with a polybasic domain and an irreversibly attached lipid instead of palmitate rendered GIRK channel closure insensitive to depalmitoylation inhibitors. Palmitate turnover therefore is required for localizing R7BP to the plasma membrane and facilitating Gi/o deactivation by R7 RGS proteins on GIRK channels. Our findings broaden the scope of biological processes regulated by palmitate turnover on specific target proteins. Inhibiting R7BP depalmitoylation may provide a means of enhancing GIRK activity in neurological disorders. PMID:24385443

  14. FOXO1 is Required for Binding of PR on IRF4, Novel Transcriptional Regulator of Endometrial Stromal Decidualization

    PubMed Central

    Vasquez, Yasmin M.; Mazur, Erik C.; Li, Xilong; Kommagani, Ramakrishna; Jiang, Lichun; Chen, Rui; Lanz, Rainer B.; Kovanci, Ertug; Gibbons, William E.

    2015-01-01

    The forkhead box O1A (FOXO1) is an early-induced target of the protein kinase A pathway during the decidualization of human endometrial stromal cells (HESCs). In this study we identified the cistrome and transcriptome of FOXO1 and its role as a transcriptional regulator of the progesterone receptor (PR). Direct targets of FOXO1 were identified by integrating RNA sequencing with chromatin immunoprecipitation followed by deep sequencing. Gene ontology analysis demonstrated that FOXO1 regulates a subset of genes in decidualization such as those involved in cancer, p53 signaling, focal adhesions, and Wnt signaling. An overlap of the FOXO1 and PR chromatin immunoprecipitation followed by deep sequencing intervals revealed the co-occupancy of FOXO1 in more than 75% of PR binding intervals. Among these intervals were highly enriched motifs for the interferon regulatory factor member 4 (IRF4). IRF4 was determined to be a genomic target of both FOXO1 and PR and also to be differentially regulated in HESCs treated with small interfering RNA targeting FOXO1 or PR prior to decidualization stimulus. Ablation of FOXO1 was found to abolish binding of PR to the shared binding interval downstream of the IRF4 gene. Finally, small interfering RNA-mediated ablation of IRF4 was shown to compromise morphological transformation of decidualized HESCs and to attenuate the expression of the decidual markers IGFBP1, PRL, and WNT4. These results provide the first evidence that FOXO1 is functionally required for the binding of PR to genomic targets. Most notably, FOXO1 and PR are required for the regulation of IRF4, a novel transcriptional regulator of decidualization in HESCs. PMID:25584414

  15. 75 FR 52622 - Amendment to the International Traffic in Arms Regulations: Removing Requirement for Prior...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-27

    ... armed forces of a foreign country (42 FR 41631, dated August 18, 1977). Also, Sec. 124.06, entitled... effective January 1, 1985 (49 FR 47682, dated December 6, 1984). Section 126.8 did not require prior... approval, was added to Sec. 126.8 in a final rule effective March 31, 1985 (50 FR 12787, dated April...

  16. 49 CFR 192.13 - What general requirements apply to pipelines regulated under this part?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false What general requirements apply to pipelines... (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY TRANSPORTATION OF NATURAL AND OTHER GAS BY PIPELINE: MINIMUM FEDERAL SAFETY...

  17. 49 CFR 192.13 - What general requirements apply to pipelines regulated under this part?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false What general requirements apply to pipelines... (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY TRANSPORTATION OF NATURAL AND OTHER GAS BY PIPELINE: MINIMUM FEDERAL SAFETY...

  18. 49 CFR 192.13 - What general requirements apply to pipelines regulated under this part?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false What general requirements apply to pipelines... (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY TRANSPORTATION OF NATURAL AND OTHER GAS BY PIPELINE: MINIMUM FEDERAL SAFETY...

  19. 76 FR 64264 - Authority to Require Supervision and Regulation of Certain Nonbank Financial Companies

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-18

    ... comment on a proposed rule that would establish these requirements. See 76 FR 7731 (February 11, 2011... advance notice of proposed rulemaking (the ``ANPR'') on October 6, 2010 (75 FR 61653), in which it... notice of proposed rulemaking (the ``NPR'') (76 FR 4555) through which it sought public comment...

  20. 75 FR 61653 - Advance Notice of Proposed Rulemaking Regarding Authority To Require Supervision and Regulation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-06

    ...Section 113 of the Dodd-Frank Wall Street Reform and Consumer Protection Act (the ``DFA'') gives the Financial Stability Oversight Council (the ``Council'') the authority to require that a nonbank financial company be supervised by the Board of Governors of the Federal Reserve System (``Board of Governors'') and subject to prudential standards if the Council determines that material financial......

  1. 49 CFR 192.13 - What general requirements apply to pipelines regulated under this part?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false What general requirements apply to pipelines... (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY TRANSPORTATION OF NATURAL AND OTHER GAS BY PIPELINE: MINIMUM FEDERAL SAFETY...

  2. 77 FR 16196 - Delaying the Compliance Date for Certain Requirements of the Regulations Implementing Titles II...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-20

    ...By this rule, the Department of Justice is proposing to extend the date for compliance with certain requirements in the 2010 Americans with Disabilities Act (ADA) Standards for Accessible Design that relate to provision of accessible entry and exit for existing swimming pools and spas. Concurrently with the publication of this Notice of Proposed Rulemaking (NPRM), the Department is publishing......

  3. 75 FR 34277 - Federal Acquisition Regulation; FAR Case 2008-007, Additional Requirements for Market Research

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-16

    ... Research AGENCIES: Department of Defense (DoD), General Services Administration (GSA), and National... executive agencies. Specifically, the head of the agency must conduct market research before issuing an... million for the procurement of items other than commercial items is required to conduct market...

  4. 75 FR 40716 - Defense Federal Acquisition Regulation Supplement; Notification Requirements for Awards of Single...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-13

    ...; Notification Requirements for Awards of Single-Source Task or Delivery Orders (DFARS Case 2009-D036) AGENCY...-Source Task or Delivery Orders.'' 10 U.S.C. 2304a(d)(3)(A) prohibits the award of a sole-source task or... agency determines in writing that-- (1) The task or delivery orders expected under the contract are...

  5. 49 CFR 195.11 - What is a regulated rural gathering line and what requirements apply?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... established under § 195.406 corresponding to— (i) A stress level greater than 20-percent of the specified minimum yield strength of the line pipe; or (ii) If the stress level is unknown or the pipeline is not... subpart H of this part, except corrosion control is not required for pipelines existing on July 3,...

  6. 49 CFR 195.11 - What is a regulated rural gathering line and what requirements apply?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... established under § 195.406 corresponding to— (i) A stress level greater than 20-percent of the specified minimum yield strength of the line pipe; or (ii) If the stress level is unknown or the pipeline is not... subpart H of this part, except corrosion control is not required for pipelines existing on July 3,...

  7. 49 CFR 195.11 - What is a regulated rural gathering line and what requirements apply?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... established under § 195.406 corresponding to— (i) A stress level greater than 20-percent of the specified minimum yield strength of the line pipe; or (ii) If the stress level is unknown or the pipeline is not... subpart H of this part, except corrosion control is not required for pipelines existing on July 3,...

  8. 49 CFR 195.11 - What is a regulated rural gathering line and what requirements apply?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... established under § 195.406 corresponding to— (i) A stress level greater than 20-percent of the specified minimum yield strength of the line pipe; or (ii) If the stress level is unknown or the pipeline is not... subpart H of this part, except corrosion control is not required for pipelines existing on July 3,...

  9. 77 FR 66464 - Federal Acquisition Regulation; Submission for OMB Review; Value Engineering Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-05

    ... published in the Federal Register at 77 FR 43076, on July 23, 2012. No comments were received. Public... Register at 77 FR 43076, on July 23, 2012. Respondents: 1,934. Responses per Respondent: 2. Annual...., Washington, DC 20417. ATTN: Hada Flowers/IC 9000-0027, Value Engineering Requirements. Instructions:...

  10. 76 FR 53886 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Special...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-30

    ... 252.217-7026, Identification of Sources of Supply; and 252.217- 7028, Over and Above Work; OMB Control... it limits the Government's liability as a related party to the work the contractor performs... above'' work before the work commences. This requirement allows the Government to review the need...